DNA polymerase beta: Difference between revisions

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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
 
| update_page = yes
{{Infobox rfam
| require_manual_inspection = no
| Name = Stem loopII regulatory element in POLB
| update_protein_box = yes
| image = RF01455.png
| update_summary = yes
| width = 200
| update_citations = yes
| caption = Predicted secondary structure of the stem loopII (M2) regulatory element in POLB
}}<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
| Symbol = POLB
{{GNF_Protein_box
| AltSymbols =  
| image = PBB_Protein_POLB_image.jpg
| Rfam = RF01455
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1bno.
| miRBase =
| PDB = {{PDB2|1bno}}, {{PDB2|1bnp}}, {{PDB2|1bpb}}, {{PDB2|1bpd}}, {{PDB2|1bpe}}, {{PDB2|1bpx}}, {{PDB2|1bpy}}, {{PDB2|1bpz}}, {{PDB2|1dk2}}, {{PDB2|1dk3}}, {{PDB2|1huo}}, {{PDB2|1huz}}, {{PDB2|1jn3}}, {{PDB2|1mq2}}, {{PDB2|1mq3}}, {{PDB2|1nom}}, {{PDB2|1rpl}}, {{PDB2|1tv9}}, {{PDB2|1tva}}, {{PDB2|1zjm}}, {{PDB2|1zjn}}, {{PDB2|1zqa}}, {{PDB2|1zqb}}, {{PDB2|1zqc}}, {{PDB2|1zqd}}, {{PDB2|1zqe}}, {{PDB2|1zqf}}, {{PDB2|1zqg}}, {{PDB2|1zqh}}, {{PDB2|1zqi}}, {{PDB2|1zqj}}, {{PDB2|1zqk}}, {{PDB2|1zql}}, {{PDB2|1zqm}}, {{PDB2|1zqn}}, {{PDB2|1zqo}}, {{PDB2|1zqp}}, {{PDB2|1zqq}}, {{PDB2|1zqr}}, {{PDB2|1zqs}}, {{PDB2|1zqt}}, {{PDB2|1zqu}}, {{PDB2|1zqv}}, {{PDB2|1zqw}}, {{PDB2|1zqx}}, {{PDB2|1zqy}}, {{PDB2|1zqz}}, {{PDB2|2bpc}}, {{PDB2|2bpf}}, {{PDB2|2bpg}}, {{PDB2|2fmp}}, {{PDB2|2fmq}}, {{PDB2|2fms}}, {{PDB2|2i9g}}, {{PDB2|2iso}}, {{PDB2|2isp}}, {{PDB2|2p66}}, {{PDB2|7ice}}, {{PDB2|7icf}}, {{PDB2|7icg}}, {{PDB2|7ich}}, {{PDB2|7ici}}, {{PDB2|7icj}}, {{PDB2|7ick}}, {{PDB2|7icl}}, {{PDB2|7icm}}, {{PDB2|7icn}}, {{PDB2|7ico}}, {{PDB2|7icp}}, {{PDB2|7icq}}, {{PDB2|7icr}}, {{PDB2|7ics}}, {{PDB2|7ict}}, {{PDB2|7icu}}, {{PDB2|7icv}}, {{PDB2|8ica}}, {{PDB2|8icb}}, {{PDB2|8icc}}, {{PDB2|8ice}}, {{PDB2|8icf}}, {{PDB2|8icg}}, {{PDB2|8ich}}, {{PDB2|8ici}}, {{PDB2|8icj}}, {{PDB2|8ick}}, {{PDB2|8icl}}, {{PDB2|8icm}}, {{PDB2|8icn}}, {{PDB2|8ico}}, {{PDB2|8icp}}, {{PDB2|8icq}}, {{PDB2|8icr}}, {{PDB2|8ics}}, {{PDB2|8ict}}, {{PDB2|8icu}}, {{PDB2|8icv}}, {{PDB2|8icw}}, {{PDB2|8icx}}, {{PDB2|8icy}}, {{PDB2|8icz}}, {{PDB2|9ica}}, {{PDB2|9icb}}, {{PDB2|9icc}}, {{PDB2|9ice}}, {{PDB2|9icf}}, {{PDB2|9icg}}, {{PDB2|9ich}}, {{PDB2|9ici}}, {{PDB2|9icj}}, {{PDB2|9ick}}, {{PDB2|9icl}}, {{PDB2|9icm}}, {{PDB2|9icn}}, {{PDB2|9ico}}, {{PDB2|9icp}}, {{PDB2|9icq}}, {{PDB2|9icr}}, {{PDB2|9ics}}, {{PDB2|9ict}}, {{PDB2|9icu}}, {{PDB2|9icv}}, {{PDB2|9icw}}, {{PDB2|9icx}}, {{PDB2|9icy}}
| miRBase_family =
| Name = Polymerase (DNA directed), beta
| RNA_type = [[Cis-reg]]
| HGNCid = 9174
| Tax_domain = [[Mammalia]]
| Symbol = POLB
| CAS_number =  
| AltSymbols =; MGC125976
| EntrezGene = 5423
| OMIM = 174760
| HGNCid = POLB
| ECnumber =
| OMIM = 174760
| Homologene = 2013
| PDB =  
| MGIid = 97740
| RefSeq = NM_002690
| GeneAtlas_image1 = PBB_GE_POLB_203616_at_tn.png
| Chromosome = 8
| Function = {{GNF_GO|id=GO:0000287 |text = magnesium ion binding}} {{GNF_GO|id=GO:0003890 |text = beta DNA polymerase activity}} {{GNF_GO|id=GO:0008017 |text = microtubule binding}} {{GNF_GO|id=GO:0016740 |text = transferase activity}} {{GNF_GO|id=GO:0016829 |text = lyase activity}} {{GNF_GO|id=GO:0031402 |text = sodium ion binding}} {{GNF_GO|id=GO:0043565 |text = sequence-specific DNA binding}}
| Arm = p
| Component = {{GNF_GO|id=GO:0005622 |text = intracellular}} {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}} {{GNF_GO|id=GO:0005876 |text = spindle microtubule}}
| Band = 11.2
| Process = {{GNF_GO|id=GO:0006261 |text = DNA-dependent DNA replication}} {{GNF_GO|id=GO:0006281 |text = DNA repair}} {{GNF_GO|id=GO:0006916 |text = anti-apoptosis}} {{GNF_GO|id=GO:0008219 |text = cell death}}
| LocusSupplementaryData =  
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 5423
    | Hs_Ensembl = ENSG00000070501
    | Hs_RefseqProtein = NP_002681
    | Hs_RefseqmRNA = NM_002690
    | Hs_GenLoc_db =
    | Hs_GenLoc_chr = 8
    | Hs_GenLoc_start = 42315131
    | Hs_GenLoc_end = 42348482
    | Hs_Uniprot = P06746
    | Mm_EntrezGene = 18970
    | Mm_Ensembl = ENSMUSG00000031536
    | Mm_RefseqmRNA = NM_011130
    | Mm_RefseqProtein = NP_035260
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 8
    | Mm_GenLoc_start = 24093675
    | Mm_GenLoc_end = 24118966
    | Mm_Uniprot = Q62085
  }}
}}
}}
'''Polymerase (DNA directed), beta''', also known as '''POLB''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: POLB polymerase (DNA directed), beta| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5423| accessdate = }}</ref>
'''DNA polymerase, beta''', also known as '''POLB''', is an [[enzyme]] present in [[eukaryotes]]. In humans, it is encoded by the  ''POLB'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: POLB polymerase (DNA directed), beta| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5423| accessdate = }}</ref>
 
== Function ==
In [[Eukaryote|eukaryotic]] cells, DNA polymerase beta (POLB) performs [[base excision repair]] (BER) required for [[DNA]] maintenance, [[DNA replication|replication]], [[Genetic recombination|recombination]], and drug resistance.<ref name="entrez" />
 
The [[mitochondrial DNA]] of mammalian cells is constantly under attack from [[reactive oxygen species|oxygen radicals]] released during [[cellular respiration|ATP production]].  Mammalian cell mitochondria contain an efficient [[base excision repair]] system employing POLB that removes some frequent [[DNA oxidation|oxidative DNA damages]].<ref name="pmid29100041">{{cite journal |vauthors=Prasad R, Çağlayan M, Dai DP, Nadalutti CA, Zhao ML, Gassman NR, Janoshazi AK, Stefanick DF, Horton JK, Krasich R, Longley MJ, Copeland WC, Griffith JD, Wilson SH |title=DNA polymerase β: A missing link of the base excision repair machinery in mammalian mitochondria |journal=DNA Repair (Amst.) |volume=60 |issue= |pages=77–88 |date=December 2017 |pmid=29100041 |doi=10.1016/j.dnarep.2017.10.011 |url=}}</ref>  POLB thus has a key role in maintaining the stability of the mitochondrial [[genome]].<ref name="pmid29100041" />
 
An analysis of the fidelity of [[DNA replication]] by polymerase beta in the [[neuron]]s from young and very aged mice indicated that [[ageing|aging]] has no significant effect on the fidelity of DNA synthesis by polymerase beta.<ref name="pmid3161998">{{cite journal |vauthors=Subba Rao K, Martin GM, Loeb LA |title=Fidelity of DNA polymerase-beta in neurons from young and very aged mice |journal=J. Neurochem. |volume=45 |issue=4 |pages=1273–8 |date=October 1985 |pmid=3161998 |doi= |url=}}</ref>  This finding was considered to provide evidence against the error catastrophe theory of aging.<ref name="pmid3161998" /><ref name="pmid4591306">{{cite journal |vauthors=Orgel LE |title=Ageing of clones of mammalian cells |journal=Nature |volume=243 |issue=5408 |pages=441–5 |date=June 1973 |pmid=4591306 |doi= |url=}}</ref>
 
== Regulation of expression ==
DNA polymerase beta maintains genome integrity by participating in [[base excision repair]]. Overexpression of POLB [[mRNA]] has been correlated with a number of cancer types, whereas deficiencies in POLB results in hypersensitivity to [[alkylating agents]], induced [[apoptosis]], and chromosomal breaking [ref7]. Therefore, it is essential that POLB expression is tightly regulated.<ref name="pmid9770529">{{cite journal | vauthors = Canitrot Y, Cazaux C, Fréchet M, Bouayadi K, Lesca C, Salles B, Hoffmann JS | title = Overexpression of DNA polymerase beta in cell results in a mutator phenotype and a decreased sensitivity to anticancer drugs | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 21 | pages = 12586–90 | date = Oct 1998 | pmid = 9770529 | pmc = 22874 | doi = 10.1073/pnas.95.21.12586 }}</ref><ref name="pmid12067997">{{cite journal | vauthors = Bergoglio V, Pillaire MJ, Lacroix-Triki M, Raynaud-Messina B, Canitrot Y, Bieth A, Garès M, Wright M, Delsol G, Loeb LA, Cazaux C, Hoffmann JS | title = Deregulated DNA polymerase beta induces chromosome instability and tumorigenesis | journal = Cancer Research | volume = 62 | issue = 12 | pages = 3511–4 | date = Jun 2002 | pmid = 12067997 | doi =  }}</ref><ref name="pmid11593426">{{cite journal | vauthors = Bergoglio V, Canitrot Y, Hogarth L, Minto L, Howell SB, Cazaux C, Hoffmann JS | title = Enhanced expression and activity of DNA polymerase beta in human ovarian tumor cells: impact on sensitivity towards antitumor agents | journal = Oncogene | volume = 20 | issue = 43 | pages = 6181–7 | date = Sep 2001 | pmid = 11593426 | doi = 10.1038/sj.onc.1204743 }}</ref><ref name="pmid10357787">{{cite journal | vauthors = Srivastava DK, Husain I, Arteaga CL, Wilson SH | title = DNA polymerase beta expression differences in selected human tumors and cell lines | journal = Carcinogenesis | volume = 20 | issue = 6 | pages = 1049–54 | date = Jun 1999 | pmid = 10357787 | doi = 10.1093/carcin/20.6.1049 }}</ref>
 
POLB gene is upregulated by [[CREB1]] [[transcription factor]]'s binding to the [[cAMP response element]](CRE) present in the promoter of the POLB gene in response to exposure to alkylating agents.<ref name="pmid12674496">{{cite journal | vauthors = He F, Yang XP, Srivastava DK, Wilson SH | title = DNA polymerase beta gene expression: the promoter activator CREB-1 is upregulated in Chinese hamster ovary cells by DNA alkylating agent-induced stress | journal = Biological Chemistry | volume = 384 | issue = 1 | pages = 19–23 | date = Jan 2003 | pmid = 12674496 | doi = 10.1515/BC.2003.003 }}</ref><ref name="pmid8702497">{{cite journal | vauthors = Narayan S, He F, Wilson SH | title = Activation of the human DNA polymerase beta promoter by a DNA-alkylating agent through induced phosphorylation of cAMP response element-binding protein-1 | journal = The Journal of Biological Chemistry | volume = 271 | issue = 31 | pages = 18508–13 | date = Aug 1996 | pmid = 8702497 | doi = 10.1074/jbc.271.31.18508 }}</ref> POLB gene expression is also regulated at the post transcriptional level as the 3’[[Untranslated Region|UTR]] of the POLB mRNA has been shown to contain three [[stem-loop]] structures that influence gene expression.<ref name="pmid17704138">{{cite journal | vauthors = Sarnowska E, Grzybowska EA, Sobczak K, Konopinski R, Wilczynska A, Szwarc M, Sarnowski TJ, Krzyzosiak WJ, Siedlecki JA | title = Hairpin structure within the 3'UTR of DNA polymerase beta mRNA acts as a post-transcriptional regulatory element and interacts with Hax-1 | journal = Nucleic Acids Research | volume = 35 | issue = 16 | pages = 5499–510 | year = 2007 | pmid = 17704138 | pmc = 2018635 | doi = 10.1093/nar/gkm502 }}</ref> These three-stem loop structures are known as M1, M2, and M3, where M2 and M3 have a key role in gene regulation. M3 contributes to gene expression, as it contains the [[polyadenylation]] signal followed by the cleavage and polyadenylation site, thereby contributing to [[pre-mRNA processing]]. M2 has been shown to be evolutionary conserved, and, through mutagenesis, it was shown that this stem loop structure acts as a RNA destabilizing element.
 
In addition to these [[cis-regulatory element]]s present within the 3’UTR a [[trans-acting]] protein, [[HAX1]] is thought to contribute to the regulation of gene expression. Yeast three-hybrid assays have shown that this protein binds to the stem loops within the 3’UTR of the POLB mRNA, however the exact mechanism in how this protein regulates gene expression is still to be determined.
 
== Interactions ==
DNA polymerase beta has been shown to [[Protein-protein interaction|interact]] with [[PNKP]]<ref name=pmid11163244>{{cite journal | vauthors = Whitehouse CJ, Taylor RM, Thistlethwaite A, Zhang H, Karimi-Busheri F, Lasko DD, Weinfeld M, Caldecott KW | title = XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair | journal = Cell | volume = 104 | issue = 1 | pages = 107–17 | date = Jan 2001 | pmid = 11163244 | doi = 10.1016/S0092-8674(01)00195-7 }}</ref> and [[XRCC1]].<ref name=pmid15520167>{{cite journal | vauthors = Wang L, Bhattacharyya N, Chelsea DM, Escobar PF, Banerjee S | title = A novel nuclear protein, MGC5306 interacts with DNA polymerase beta and has a potential role in cellular phenotype | journal = Cancer Research | volume = 64 | issue = 21 | pages = 7673–7 | date = Nov 2004 | pmid = 15520167 | doi = 10.1158/0008-5472.CAN-04-2801 }}</ref><ref name=pmid15107487>{{cite journal | vauthors = Fan J, Otterlei M, Wong HK, Tomkinson AE, Wilson DM | title = XRCC1 co-localizes and physically interacts with PCNA | journal = Nucleic Acids Research | volume = 32 | issue = 7 | pages = 2193–201 | year = 2004 | pmid = 15107487 | pmc = 407833 | doi = 10.1093/nar/gkh556 }}</ref><ref name=pmid8978692>{{cite journal | vauthors = Kubota Y, Nash RA, Klungland A, Schär P, Barnes DE, Lindahl T | title = Reconstitution of DNA base excision-repair with purified human proteins: interaction between DNA polymerase beta and the XRCC1 protein | journal = The EMBO Journal | volume = 15 | issue = 23 | pages = 6662–70 | date = Dec 1996 | pmid = 8978692 | pmc = 452490 }}</ref><ref name=pmid11467963>{{cite journal | vauthors = Bhattacharyya N, Banerjee S | title = A novel role of XRCC1 in the functions of a DNA polymerase beta variant | journal = Biochemistry | volume = 40 | issue = 30 | pages = 9005–13 | date = Jul 2001 | pmid = 11467963 | doi = 10.1021/bi0028789 }}</ref>
 
== See also ==
* [[Polymerase (DNA directed), alpha 1|POLA1]]
* [[POLA2]]
 
==Model organisms==
[[Model organism]]s have been used in the study of POLB function. A conditional [[knockout mouse]] line called ''Polb<sup>tm1a(KOMP)Wtsi</sup>'' was generated at the [[Wellcome Trust Sanger Institute]].<ref name="mgp_reference">{{cite journal |title=The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice |author=Gerdin AK |year=2010 |journal=Acta Ophthalmologica|volume=88 |pages=925–7|doi=10.1111/j.1755-3768.2010.4142.x }}</ref> Male and female animals underwent a standardized [[phenotypic screen]]<ref name="IMPCsearch_ref">{{cite web |url=http://www.mousephenotype.org/data/search?q=Polb#fq=*:*&facet=gene |title=International Mouse Phenotyping Consortium}}</ref> to determine the effects of deletion.<ref name="pmid21677750">{{cite journal | vauthors = Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A | title = A conditional knockout resource for the genome-wide study of mouse gene function | journal = Nature | volume = 474 | issue = 7351 | pages = 337–42 | date = Jun 2011 | pmid = 21677750 | pmc = 3572410 | doi = 10.1038/nature10163 }}</ref><ref name="mouse_library">{{cite journal | vauthors = Dolgin E | title = Mouse library set to be knockout | journal = Nature | volume = 474 | issue = 7351 | pages = 262–3 | date = Jun 2011 | pmid = 21677718 | doi = 10.1038/474262a }}</ref><ref name="mouse_for_all_reasons">{{cite journal | vauthors = Collins FS, Rossant J, Wurst W | title = A mouse for all reasons | journal = Cell | volume = 128 | issue = 1 | pages = 9–13 | date = Jan 2007 | pmid = 17218247 | doi = 10.1016/j.cell.2006.12.018 }}</ref><ref name="pmid23870131">{{cite journal | vauthors = White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP | title = Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes | journal = Cell | volume = 154 | issue = 2 | pages = 452–64 | date = Jul 2013 | pmid = 23870131 | pmc = 3717207 | doi = 10.1016/j.cell.2013.06.022 }}</ref> Additional screens performed:  - In-depth immunological phenotyping<ref name="iii_ref">{{cite web |url= http://www.immunophenotyping.org/data/search?keys=Polb&field_gene_construct_tid=All |title=Infection and Immunity Immunophenotyping (3i) Consortium}}</ref>
{| class="wikitable sortable collapsible collapsed" border="1" cellpadding="2" style="float: left;" |
|+ ''Polb'' knockout mouse phenotype
|-
! Characteristic!! Phenotype
|-
| colspan=2; style="text-align: center;" | All data available at.<ref name="IMPCsearch_ref"/><ref name="iii_ref" />{
 
|-
| Peripheral blood leukocytes 6 Weeks || bgcolor="#488ED3"|Normal
 
|-
| ''[[Haematology]]'' 6 Weeks || bgcolor="#488ED3"|Normal
 
|-
| Homozygous viability at P14 || bgcolor="#C40000"|Abnormal
 
|-
| [[Recessive]] lethal study || bgcolor="#C40000"|Abnormal
 
|-
| Body weight || bgcolor="#488ED3"|Normal
 
|-
| Neurological assessment || bgcolor="#488ED3"|Normal


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
|-
{{PBB_Summary
| Grip strength || bgcolor="#488ED3"|Normal
| section_title =  
 
| summary_text = In eukaryotic cells, DNA polymerase beta (POLB) performs base excision repair (BER) required for DNA maintenance, replication, recombination, and drug resistance. Also see POLA (MIM 312040).[supplied by OMIM]<ref name="entrez">{{cite web | title = Entrez Gene: POLB polymerase (DNA directed), beta| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5423| accessdate = }}</ref>
|-
}}
| [[Dysmorphology]] || bgcolor="#488ED3"|Normal
 
|-
| [[Indirect calorimetry]] || bgcolor="#488ED3"|Normal
 
|-
| [[Glucose tolerance test]] || bgcolor="#488ED3"|Normal
 
|-
| [[Auditory brainstem response]] || bgcolor="#488ED3"|Normal
 
|-
| [[Dual-energy X-ray absorptiometry|DEXA]] || bgcolor="#488ED3"|Normal
 
|-
| Eye morphology || bgcolor="#488ED3"|Normal
 
|-
| [[Clinical chemistry]] || bgcolor="#488ED3"|Normal
 
|-
| ''[[Haematology]]'' 16 Weeks || bgcolor="#488ED3"|Normal
 
|-
| Peripheral blood leukocytes 16 Weeks || bgcolor="#488ED3"|Normal
 
|-
| Heart weight || bgcolor="#488ED3"|Normal
 
|-
| ''[[Salmonella]]'' infection || bgcolor="#488ED3"|Normal
 
|-
| Cytotoxic T Cell Function || bgcolor="#488ED3"|Normal
 
|-
| Spleen Immunophenotyping || bgcolor="#488ED3"|Normal
 
|-
| Mesenteric Lymph Node Immunophenotyping || bgcolor="#488ED3"|Normal
 
|-
| Bone Marrow Immunophenotyping || bgcolor="#488ED3"|Normal
 
|-
| Epidermal Immune Composition || bgcolor="#488ED3"|Normal
 
|-
| Trichuris Challenge || bgcolor="#488ED3"|Normal
 
|-
|}
{{clear|left}}
 
== References ==
{{reflist|35em}}


==References==
== Further reading ==
{{reflist|2}}
{{refbegin |35em}}
==Further reading==
* {{cite journal | vauthors = Date T, Tanihara K, Yamamoto S, Nomura N, Matsukage A | title = Two regions in human DNA polymerase beta mRNA suppress translation in Escherichia coli | journal = Nucleic Acids Research | volume = 20 | issue = 18 | pages = 4859–64 | date = Sep 1992 | pmid = 1408801 | pmc = 334243 | doi = 10.1093/nar/20.18.4859 }}
{{refbegin | 2}}
* {{cite journal | vauthors = Wang L, Patel U, Ghosh L, Banerjee S | title = DNA polymerase beta mutations in human colorectal cancer | journal = Cancer Research | volume = 52 | issue = 17 | pages = 4824–7 | date = Sep 1992 | pmid = 1511447 | doi =  }}
{{PBB_Further_reading
* {{cite journal | vauthors = Tokui T, Inagaki M, Nishizawa K, Yatani R, Kusagawa M, Ajiro K, Nishimoto Y, Date T, Matsukage A | title = Inactivation of DNA polymerase beta by in vitro phosphorylation with protein kinase C | journal = The Journal of Biological Chemistry | volume = 266 | issue = 17 | pages = 10820–4 | date = Jun 1991 | pmid = 2040602 | doi =  }}
| citations =
* {{cite journal | vauthors = SenGupta DN, Zmudzka BZ, Kumar P, Cobianchi F, Skowronski J, Wilson SH | title = Sequence of human DNA polymerase beta mRNA obtained through cDNA cloning | journal = Biochemical and Biophysical Research Communications | volume = 136 | issue = 1 | pages = 341–7 | date = Apr 1986 | pmid = 2423078 | doi = 10.1016/0006-291X(86)90916-2 }}
*{{cite journal | author=Date T, Tanihara K, Yamamoto S, ''et al.'' |title=Two regions in human DNA polymerase beta mRNA suppress translation in Escherichia coli. |journal=Nucleic Acids Res. |volume=20 |issue= 18 |pages= 4859-64 |year= 1992 |pmid= 1408801 |doi= }}
* {{cite journal | vauthors = Zmudzka BZ, Fornace A, Collins J, Wilson SH | title = Characterization of DNA polymerase beta mRNA: cell-cycle and growth response in cultured human cells | journal = Nucleic Acids Research | volume = 16 | issue = 20 | pages = 9587–96 | date = Oct 1988 | pmid = 2460824 | pmc = 338765 | doi = 10.1093/nar/16.20.9587 }}
*{{cite journal | author=Wang L, Patel U, Ghosh L, Banerjee S |title=DNA polymerase beta mutations in human colorectal cancer. |journal=Cancer Res. |volume=52 |issue= 17 |pages= 4824-7 |year= 1992 |pmid= 1511447 |doi=  }}
* {{cite journal | vauthors = Widen SG, Kedar P, Wilson SH | title = Human beta-polymerase gene. Structure of the 5'-flanking region and active promoter | journal = The Journal of Biological Chemistry | volume = 263 | issue = 32 | pages = 16992–8 | date = Nov 1988 | pmid = 3182828 | doi =  }}
*{{cite journal | author=Tokui T, Inagaki M, Nishizawa K, ''et al.'' |title=Inactivation of DNA polymerase beta by in vitro phosphorylation with protein kinase C. |journal=J. Biol. Chem. |volume=266 |issue= 17 |pages= 10820-4 |year= 1991 |pmid= 2040602 |doi=  }}
* {{cite journal | vauthors = Abbotts J, SenGupta DN, Zmudzka B, Widen SG, Notario V, Wilson SH | title = Expression of human DNA polymerase beta in Escherichia coli and characterization of the recombinant enzyme | journal = Biochemistry | volume = 27 | issue = 3 | pages = 901–9 | date = Feb 1988 | pmid = 3284575 | doi = 10.1021/bi00403a010 }}
*{{cite journal | author=SenGupta DN, Zmudzka BZ, Kumar P, ''et al.'' |title=Sequence of human DNA polymerase beta mRNA obtained through cDNA cloning. |journal=Biochem. Biophys. Res. Commun. |volume=136 |issue= 1 |pages= 341-7 |year= 1986 |pmid= 2423078 |doi= }}
* {{cite journal | vauthors = Dobashi Y, Kubota Y, Shuin T, Torigoe S, Yao M, Hosaka M | title = Polymorphisms in the human DNA polymerase beta gene | journal = Human Genetics | volume = 95 | issue = 4 | pages = 389–90 | date = Apr 1995 | pmid = 7705833 | doi = 10.1007/bf00208961 }}
*{{cite journal | author=Zmudzka BZ, Fornace A, Collins J, Wilson SH |title=Characterization of DNA polymerase beta mRNA: cell-cycle and growth response in cultured human cells. |journal=Nucleic Acids Res. |volume=16 |issue= 20 |pages= 9587-96 |year= 1988 |pmid= 2460824 |doi= }}
* {{cite journal | vauthors = Chyan YJ, Ackerman S, Shepherd NS, McBride OW, Widen SG, Wilson SH, Wood TG | title = The human DNA polymerase beta gene structure. Evidence of alternative splicing in gene expression | journal = Nucleic Acids Research | volume = 22 | issue = 14 | pages = 2719–25 | date = Jul 1994 | pmid = 7914364 | pmc = 308239 | doi = 10.1093/nar/22.14.2719 }}
*{{cite journal | author=Widen SG, Kedar P, Wilson SH |title=Human beta-polymerase gene. Structure of the 5'-flanking region and active promoter. |journal=J. Biol. Chem. |volume=263 |issue= 32 |pages= 16992-8 |year= 1988 |pmid= 3182828 |doi=  }}
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1-2 | pages = 171–4 | date = Jan 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
*{{cite journal | author=Abbotts J, SenGupta DN, Zmudzka B, ''et al.'' |title=Expression of human DNA polymerase beta in Escherichia coli and characterization of the recombinant enzyme. |journal=Biochemistry |volume=27 |issue= 3 |pages= 901-9 |year= 1988 |pmid= 3284575 |doi= }}
* {{cite journal | vauthors = Chang M, Burmer GC, Sweasy J, Loeb LA, Edelhoff S, Disteche CM, Yu CE, Anderson L, Oshima J, Nakura J | title = Evidence against DNA polymerase beta as a candidate gene for Werner syndrome | journal = Human Genetics | volume = 93 | issue = 5 | pages = 507–12 | date = May 1994 | pmid = 8168825 | doi = 10.1007/bf00202813 }}
*{{cite journal | author=Dobashi Y, Kubota Y, Shuin T, ''et al.'' |title=Polymorphisms in the human DNA polymerase beta gene. |journal=Hum. Genet. |volume=95 |issue= 4 |pages= 389-90 |year= 1995 |pmid= 7705833 |doi= }}
* {{cite journal | vauthors = Chyan YJ, Strauss PR, Wood TG, Wilson SH | title = Identification of novel mRNA isoforms for human DNA polymerase beta | journal = DNA and Cell Biology | volume = 15 | issue = 8 | pages = 653–9 | date = Aug 1996 | pmid = 8769567 | doi = 10.1089/dna.1996.15.653 }}
*{{cite journal | author=Chyan YJ, Ackerman S, Shepherd NS, ''et al.'' |title=The human DNA polymerase beta gene structure. Evidence of alternative splicing in gene expression. |journal=Nucleic Acids Res. |volume=22 |issue= 14 |pages= 2719-25 |year= 1994 |pmid= 7914364 |doi= }}
* {{cite journal | vauthors = Pelletier H, Sawaya MR, Wolfle W, Wilson SH, Kraut J | title = Crystal structures of human DNA polymerase beta complexed with DNA: implications for catalytic mechanism, processivity, and fidelity | journal = Biochemistry | volume = 35 | issue = 39 | pages = 12742–61 | date = Oct 1996 | pmid = 8841118 | doi = 10.1021/bi952955d }}
*{{cite journal | author=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171-4 |year= 1994 |pmid= 8125298 |doi= }}
* {{cite journal | vauthors = Pelletier H, Sawaya MR, Wolfle W, Wilson SH, Kraut J | title = A structural basis for metal ion mutagenicity and nucleotide selectivity in human DNA polymerase beta | journal = Biochemistry | volume = 35 | issue = 39 | pages = 12762–77 | date = Oct 1996 | pmid = 8841119 | doi = 10.1021/bi9529566 }}
*{{cite journal | author=Chang M, Burmer GC, Sweasy J, ''et al.'' |title=Evidence against DNA polymerase beta as a candidate gene for Werner syndrome. |journal=Hum. Genet. |volume=93 |issue= 5 |pages= 507-12 |year= 1994 |pmid= 8168825 |doi= }}
* {{cite journal | vauthors = Pelletier H, Sawaya MR | title = Characterization of the metal ion binding helix-hairpin-helix motifs in human DNA polymerase beta by X-ray structural analysis | journal = Biochemistry | volume = 35 | issue = 39 | pages = 12778–87 | date = Oct 1996 | pmid = 8841120 | doi = 10.1021/bi960790i }}
*{{cite journal |author=Chyan YJ, Strauss PR, Wood TG, Wilson SH |title=Identification of novel mRNA isoforms for human DNA polymerase beta. |journal=DNA Cell Biol. |volume=15 |issue= 8 |pages= 653-9 |year= 1996 |pmid= 8769567 |doi= }}
* {{cite journal | vauthors = Kubota Y, Nash RA, Klungland A, Schär P, Barnes DE, Lindahl T | title = Reconstitution of DNA base excision-repair with purified human proteins: interaction between DNA polymerase beta and the XRCC1 protein | journal = The EMBO Journal | volume = 15 | issue = 23 | pages = 6662–70 | date = Dec 1996 | pmid = 8978692 | pmc = 452490 | doi =  }}
*{{cite journal | author=Pelletier H, Sawaya MR, Wolfle W, ''et al.'' |title=Crystal structures of human DNA polymerase beta complexed with DNA: implications for catalytic mechanism, processivity, and fidelity. |journal=Biochemistry |volume=35 |issue= 39 |pages= 12742-61 |year= 1996 |pmid= 8841118 |doi= 10.1021/bi952955d }}
* {{cite journal | vauthors = Bennett RA, Wilson DM, Wong D, Demple B | title = Interaction of human apurinic endonuclease and DNA polymerase beta in the base excision repair pathway | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 14 | pages = 7166–9 | date = Jul 1997 | pmid = 9207062 | pmc = 23779 | doi = 10.1073/pnas.94.14.7166 }}
*{{cite journal | author=Pelletier H, Sawaya MR, Wolfle W, ''et al.'' |title=A structural basis for metal ion mutagenicity and nucleotide selectivity in human DNA polymerase beta. |journal=Biochemistry |volume=35 |issue= 39 |pages= 12762-77 |year= 1996 |pmid= 8841119 |doi= 10.1021/bi9529566 }}
* {{cite journal | vauthors = Sawaya MR, Prasad R, Wilson SH, Kraut J, Pelletier H | title = Crystal structures of human DNA polymerase beta complexed with gapped and nicked DNA: evidence for an induced fit mechanism | journal = Biochemistry | volume = 36 | issue = 37 | pages = 11205–15 | date = Sep 1997 | pmid = 9287163 | doi = 10.1021/bi9703812 }}
*{{cite journal | author=Pelletier H, Sawaya MR |title=Characterization of the metal ion binding helix-hairpin-helix motifs in human DNA polymerase beta by X-ray structural analysis. |journal=Biochemistry |volume=35 |issue= 39 |pages= 12778-87 |year= 1996 |pmid= 8841120 |doi= 10.1021/bi960790i }}
* {{cite journal | vauthors = Bhattacharyya N, Banerjee S | title = A variant of DNA polymerase beta acts as a dominant negative mutant | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 19 | pages = 10324–9 | date = Sep 1997 | pmid = 9294209 | pmc = 23361 | doi = 10.1073/pnas.94.19.10324 }}
*{{cite journal | author=Kubota Y, Nash RA, Klungland A, ''et al.'' |title=Reconstitution of DNA base excision-repair with purified human proteins: interaction between DNA polymerase beta and the XRCC1 protein. |journal=EMBO J. |volume=15 |issue= 23 |pages= 6662-70 |year= 1997 |pmid= 8978692 |doi=  }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1-2 | pages = 149–56 | date = Oct 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
*{{cite journal | author=Bennett RA, Wilson DM, Wong D, Demple B |title=Interaction of human apurinic endonuclease and DNA polymerase beta in the base excision repair pathway. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=94 |issue= 14 |pages= 7166-9 |year= 1997 |pmid= 9207062 |doi= }}
* {{cite journal | vauthors = Tan XH, Zhao M, Pan KF, Dong Y, Dong B, Feng GJ, Jia G, Lu YY | title = Frequent mutation related with overexpression of DNA polymerase beta in primary tumors and precancerous lesions of human stomach | journal = Cancer Letters | volume = 220 | issue = 1 | pages = 101–14 | date = Mar 2005 | pmid = 15737693 | pmc =  | doi = 10.1016/j.canlet.2004.07.049 }}
*{{cite journal | author=Sawaya MR, Prasad R, Wilson SH, ''et al.'' |title=Crystal structures of human DNA polymerase beta complexed with gapped and nicked DNA: evidence for an induced fit mechanism. |journal=Biochemistry |volume=36 |issue= 37 |pages= 11205-15 |year= 1997 |pmid= 9287163 |doi= 10.1021/bi9703812 }}
*{{cite journal | author=Bhattacharyya N, Banerjee S |title=A variant of DNA polymerase beta acts as a dominant negative mutant. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=94 |issue= 19 |pages= 10324-9 |year= 1997 |pmid= 9294209 |doi= }}
*{{cite journal | author=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, ''et al.'' |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1-2 |pages= 149-56 |year= 1997 |pmid= 9373149 |doi= }}
}}
{{refend}}
{{refend}}


{{protein-stub}}
== External links ==
{{WikiDoc Sources}}
*[http://rfam.org/family/RF01455 Rfam entry for the stem loopII (M2) regulatory element in POLB]
 
{{PDB Gallery|geneid=5423}}
 
[[Category:DNA repair]]
[[Category:DNA-binding proteins]]

Latest revision as of 12:47, 15 January 2019

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

n/a

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human
Stem loopII regulatory element in POLB
File:RF01455.png
Predicted secondary structure of the stem loopII (M2) regulatory element in POLB
Identifiers
SymbolPOLB
RfamRF01455
Entrez5423
HUGOPOLB
OMIM174760
RefSeqNM_002690
Other data
RNA typeCis-reg
Domain(s)Mammalia
LocusChr. 8 p11.2
PDB structuresPDBe

DNA polymerase, beta, also known as POLB, is an enzyme present in eukaryotes. In humans, it is encoded by the POLB gene.[1]

Function

In eukaryotic cells, DNA polymerase beta (POLB) performs base excision repair (BER) required for DNA maintenance, replication, recombination, and drug resistance.[1]

The mitochondrial DNA of mammalian cells is constantly under attack from oxygen radicals released during ATP production. Mammalian cell mitochondria contain an efficient base excision repair system employing POLB that removes some frequent oxidative DNA damages.[2] POLB thus has a key role in maintaining the stability of the mitochondrial genome.[2]

An analysis of the fidelity of DNA replication by polymerase beta in the neurons from young and very aged mice indicated that aging has no significant effect on the fidelity of DNA synthesis by polymerase beta.[3] This finding was considered to provide evidence against the error catastrophe theory of aging.[3][4]

Regulation of expression

DNA polymerase beta maintains genome integrity by participating in base excision repair. Overexpression of POLB mRNA has been correlated with a number of cancer types, whereas deficiencies in POLB results in hypersensitivity to alkylating agents, induced apoptosis, and chromosomal breaking [ref7]. Therefore, it is essential that POLB expression is tightly regulated.[5][6][7][8]

POLB gene is upregulated by CREB1 transcription factor's binding to the cAMP response element(CRE) present in the promoter of the POLB gene in response to exposure to alkylating agents.[9][10] POLB gene expression is also regulated at the post transcriptional level as the 3’UTR of the POLB mRNA has been shown to contain three stem-loop structures that influence gene expression.[11] These three-stem loop structures are known as M1, M2, and M3, where M2 and M3 have a key role in gene regulation. M3 contributes to gene expression, as it contains the polyadenylation signal followed by the cleavage and polyadenylation site, thereby contributing to pre-mRNA processing. M2 has been shown to be evolutionary conserved, and, through mutagenesis, it was shown that this stem loop structure acts as a RNA destabilizing element.

In addition to these cis-regulatory elements present within the 3’UTR a trans-acting protein, HAX1 is thought to contribute to the regulation of gene expression. Yeast three-hybrid assays have shown that this protein binds to the stem loops within the 3’UTR of the POLB mRNA, however the exact mechanism in how this protein regulates gene expression is still to be determined.

Interactions

DNA polymerase beta has been shown to interact with PNKP[12] and XRCC1.[13][14][15][16]

See also

Model organisms

Model organisms have been used in the study of POLB function. A conditional knockout mouse line called Polbtm1a(KOMP)Wtsi was generated at the Wellcome Trust Sanger Institute.[17] Male and female animals underwent a standardized phenotypic screen[18] to determine the effects of deletion.[19][20][21][22] Additional screens performed: - In-depth immunological phenotyping[23]

References

  1. ↑ 1.0 1.1 "Entrez Gene: POLB polymerase (DNA directed), beta".
  2. ↑ 2.0 2.1 Prasad R, Çağlayan M, Dai DP, Nadalutti CA, Zhao ML, Gassman NR, Janoshazi AK, Stefanick DF, Horton JK, Krasich R, Longley MJ, Copeland WC, Griffith JD, Wilson SH (December 2017). "DNA polymerase β: A missing link of the base excision repair machinery in mammalian mitochondria". DNA Repair (Amst.). 60: 77–88. doi:10.1016/j.dnarep.2017.10.011. PMID 29100041.
  3. ↑ 3.0 3.1 Subba Rao K, Martin GM, Loeb LA (October 1985). "Fidelity of DNA polymerase-beta in neurons from young and very aged mice". J. Neurochem. 45 (4): 1273–8. PMID 3161998.
  4. ↑ Orgel LE (June 1973). "Ageing of clones of mammalian cells". Nature. 243 (5408): 441–5. PMID 4591306.
  5. ↑ Canitrot Y, Cazaux C, Fréchet M, Bouayadi K, Lesca C, Salles B, Hoffmann JS (Oct 1998). "Overexpression of DNA polymerase beta in cell results in a mutator phenotype and a decreased sensitivity to anticancer drugs". Proceedings of the National Academy of Sciences of the United States of America. 95 (21): 12586–90. doi:10.1073/pnas.95.21.12586. PMC 22874. PMID 9770529.
  6. ↑ Bergoglio V, Pillaire MJ, Lacroix-Triki M, Raynaud-Messina B, Canitrot Y, Bieth A, Garès M, Wright M, Delsol G, Loeb LA, Cazaux C, Hoffmann JS (Jun 2002). "Deregulated DNA polymerase beta induces chromosome instability and tumorigenesis". Cancer Research. 62 (12): 3511–4. PMID 12067997.
  7. ↑ Bergoglio V, Canitrot Y, Hogarth L, Minto L, Howell SB, Cazaux C, Hoffmann JS (Sep 2001). "Enhanced expression and activity of DNA polymerase beta in human ovarian tumor cells: impact on sensitivity towards antitumor agents". Oncogene. 20 (43): 6181–7. doi:10.1038/sj.onc.1204743. PMID 11593426.
  8. ↑ Srivastava DK, Husain I, Arteaga CL, Wilson SH (Jun 1999). "DNA polymerase beta expression differences in selected human tumors and cell lines". Carcinogenesis. 20 (6): 1049–54. doi:10.1093/carcin/20.6.1049. PMID 10357787.
  9. ↑ He F, Yang XP, Srivastava DK, Wilson SH (Jan 2003). "DNA polymerase beta gene expression: the promoter activator CREB-1 is upregulated in Chinese hamster ovary cells by DNA alkylating agent-induced stress". Biological Chemistry. 384 (1): 19–23. doi:10.1515/BC.2003.003. PMID 12674496.
  10. ↑ Narayan S, He F, Wilson SH (Aug 1996). "Activation of the human DNA polymerase beta promoter by a DNA-alkylating agent through induced phosphorylation of cAMP response element-binding protein-1". The Journal of Biological Chemistry. 271 (31): 18508–13. doi:10.1074/jbc.271.31.18508. PMID 8702497.
  11. ↑ Sarnowska E, Grzybowska EA, Sobczak K, Konopinski R, Wilczynska A, Szwarc M, Sarnowski TJ, Krzyzosiak WJ, Siedlecki JA (2007). "Hairpin structure within the 3'UTR of DNA polymerase beta mRNA acts as a post-transcriptional regulatory element and interacts with Hax-1". Nucleic Acids Research. 35 (16): 5499–510. doi:10.1093/nar/gkm502. PMC 2018635. PMID 17704138.
  12. ↑ Whitehouse CJ, Taylor RM, Thistlethwaite A, Zhang H, Karimi-Busheri F, Lasko DD, Weinfeld M, Caldecott KW (Jan 2001). "XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair". Cell. 104 (1): 107–17. doi:10.1016/S0092-8674(01)00195-7. PMID 11163244.
  13. ↑ Wang L, Bhattacharyya N, Chelsea DM, Escobar PF, Banerjee S (Nov 2004). "A novel nuclear protein, MGC5306 interacts with DNA polymerase beta and has a potential role in cellular phenotype". Cancer Research. 64 (21): 7673–7. doi:10.1158/0008-5472.CAN-04-2801. PMID 15520167.
  14. ↑ Fan J, Otterlei M, Wong HK, Tomkinson AE, Wilson DM (2004). "XRCC1 co-localizes and physically interacts with PCNA". Nucleic Acids Research. 32 (7): 2193–201. doi:10.1093/nar/gkh556. PMC 407833. PMID 15107487.
  15. ↑ Kubota Y, Nash RA, Klungland A, Schär P, Barnes DE, Lindahl T (Dec 1996). "Reconstitution of DNA base excision-repair with purified human proteins: interaction between DNA polymerase beta and the XRCC1 protein". The EMBO Journal. 15 (23): 6662–70. PMC 452490. PMID 8978692.
  16. ↑ Bhattacharyya N, Banerjee S (Jul 2001). "A novel role of XRCC1 in the functions of a DNA polymerase beta variant". Biochemistry. 40 (30): 9005–13. doi:10.1021/bi0028789. PMID 11467963.
  17. ↑ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  18. ↑ 18.0 18.1 "International Mouse Phenotyping Consortium".
  19. ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  20. ↑ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  21. ↑ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  22. ↑ White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (Jul 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
  23. ↑ 23.0 23.1 "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading

External links

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