The printable version is no longer supported and may have rendering errors. Please update your browser bookmarks and please use the default browser print function instead.
Centromeres are the chromosomal domains that specify the mitotic behavior of chromosomes. The CENPA gene encodes a centromere protein which contains a histone H3 related histone fold domain that is required for targeting to the centromere. CENPA is proposed to be a component of a modified nucleosome or nucleosome-like structure in which it replaces 1 or both copies of conventional histone H3 in the (H3-H4)2 tetrameric core of the nucleosome particle. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[1]
In higher eukaryotes, the recruitment of CENP-A nucleosomes to existing centromeres is an epigenetic process, independent of the underlying DNA sequence. In S. pombe, de novo recruitment of the CENP-A to the centromere is believed to be controlled by "centromeric" heterochromatin surrounding the centromere, and by an RNAi mechanism. The RNAi is cut to form siRNA; this complexes with the protein Chp1, which then binds the centromeric heterochromatin. This helps recruit other proteins, ultimately resulting in a protein complex that forms cohesin between two sister chromatids at the centromeric heterochromatin. This cohesin is believed to be essential in replacing the centromere H3 with CENP-A. CENP-A is one of the epigenetic changes that is believed to distinguish centromeric DNA from other DNA.[2] Once the CENP-A has been added, the centromere becomes self-propagating, and the surrounding heterochromatin/RNAi mechanism is no longer necessary.[3]
↑Chueh AC, Wong LH, Wong N, Choo KH (January 2005). "Variable and hierarchical size distribution of L1-retroelement-enriched CENP-A clusters within a functional human neocentromere". Hum. Mol. Genet. 14 (1): 85–93. doi:10.1093/hmg/ddi008. PMID15537667.
Valdivia MM, Figueroa J, Iglesias C, Ortíz M (1998). "A novel centromere monospecific serum to a human autoepitope on the histone H3-like protein CENP-A". FEBS Lett. 422 (1): 5–9. doi:10.1016/S0014-5793(97)01583-4. PMID9475158.
Lomonte P, Sullivan KF, Everett RD (2001). "Degradation of nucleosome-associated centromeric histone H3-like protein CENP-A induced by herpes simplex virus type 1 protein ICP0". J. Biol. Chem. 276 (8): 5829–35. doi:10.1074/jbc.M008547200. PMID11053442.
Uren AG, Wong L, Pakusch M, Fowler KJ, Burrows FJ, Vaux DL, Choo KH (2001). "Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype". Curr. Biol. 10 (21): 1319–28. doi:10.1016/S0960-9822(00)00769-7. PMID11084331.
Saxena A, Saffery R, Wong LH, Kalitsis P, Choo KH (2002). "Centromere proteins Cenpa, Cenpb, and Bub3 interact with poly(ADP-ribose) polymerase-1 protein and are poly(ADP-ribosyl)ated". J. Biol. Chem. 277 (30): 26921–6. doi:10.1074/jbc.M200620200. PMID12011073.
Saxena A, Wong LH, Kalitsis P, Earle E, Shaffer LG, Choo KH (2003). "Poly(ADP-ribose) polymerase 2 localizes to mammalian active centromeres and interacts with PARP-1, Cenpa, Cenpb and Bub3, but not Cenpc". Hum. Mol. Genet. 11 (19): 2319–29. doi:10.1093/hmg/11.19.2319. PMID12217960.
Tomonaga T, Matsushita K, Yamaguchi S, Oohashi T, Shimada H, Ochiai T, Yoda K, Nomura F (2003). "Overexpression and mistargeting of centromere protein-A in human primary colorectal cancer". Cancer Res. 63 (13): 3511–6. PMID12839935.
Kunitoku N, Sasayama T, Marumoto T, Zhang D, Honda S, Kobayashi O, Hatakeyama K, Ushio Y, Saya H, Hirota T (2004). "CENP-A phosphorylation by Aurora-A in prophase is required for enrichment of Aurora-B at inner centromeres and for kinetochore function". Dev. Cell. 5 (6): 853–64. doi:10.1016/S1534-5807(03)00364-2. PMID14667408.
Obuse C, Yang H, Nozaki N, Goto S, Okazaki T, Yoda K (2004). "Proteomics analysis of the centromere complex from HeLa interphase cells: UV-damaged DNA binding protein 1 (DDB-1) is a component of the CEN-complex, while BMI-1 is transiently co-localized with the centromeric region in interphase". Genes Cells. 9 (2): 105–20. doi:10.1111/j.1365-2443.2004.00705.x. PMID15009096.
Yasuda S, Oceguera-Yanez F, Kato T, Okamoto M, Yonemura S, Terada Y, Ishizaki T, Narumiya S (2004). "Cdc42 and mDia3 regulate microtubule attachment to kinetochores". Nature. 428 (6984): 767–71. doi:10.1038/nature02452. PMID15085137.
Black BE, Foltz DR, Chakravarthy S, Luger K, Woods VL Jr, Cleveland DW (2004). "Structural determinants for generating centromeric chromatin". Nature. 430 (6999): 578–82. doi:10.1038/nature02766. PMID15282608.