Poly ADP ribose polymerase
Members of PARP family
The PARP family comprises 17 members (10 putative). They have all very different structures and functions in the cell.
- PARP1, PARP2, PARP3, VPARP (PARP4), Tankyrase-1 and 2 (PARP-5a or TNKS, and PARP-5b or TNKS2) and PARP10 have a confirmed PARP activity.
- Others include PARP6, TIPARP (or "PARP7"), PARP8, PARP9, PARP11, PARP12, PARP14, PARP15, and PARP16.
Role in forming polymer of ADP-ribose (PAR)
The polymer can be degraded by a specialized enzyme named PARG (poly(ADP-ribose) glycohydrolase).
Another newly discovered enzyme can degrade PAR and is unrelated to PARG. This enzyme is called ARH3 (ADPRHL2).
Role in repairing DNA nicks
One important function of PARP is assisting in the repair of single-strand DNA nicks. It binds sites with single strand breaks through its N-terminal zinc fingers and will recruit XRCC1, DNA ligase III, DNA polymerase beta and a kinase to the nick. This is called base excision repair (BER). PARP-2 has been shown to oligomerize with PARP-1 and therefore is also implicated in BER. The oligomerization has also been shown to stimulate PARP catalytic activity. PARP-1 is also known for its role in transcription through remodelling of chromatin by PARylating histones and relaxing chromatin structure, thus allowing transcription complex to access genes.
Role of tankyrases
The tankyrases are PARPs that comprise ankyrin repeats, oligomerization domain (SAM) and a PARP catalytic domain (PCD). Tankyrases are also known as PARP-5a and PARP-5b. Through their SAM domain and ANKs they can oligomerize and interact with many other proteins, such as TAB182 (TNKS1BP1), GRB14, IRAP, NuMa, EBNA-1, and Mcl-1. They have multiple roles in the cell, vesicular trafficing through its interaction in GLUT4 vesicle (GSVs) with insulin responsive amino peptidase (IRAP). It also plays a role in spindle assembly through its interaction with nuclear mitotic apparatus (NuMa) therefore allowing bipolarity. In the absence of TNKs mitosis arrest is observed in pre-anaphase through Mad2 kinetochore checkpoint. TNKs can also PARsylate Mcl-1L and Mcl-1S and inhibit both their pro and anti apoptotic function. Relevance of this is not yet known.
- Entry for a PARP immunoassay at bioreagents.com
- PARP - Poly (ADP-ribose) polymerase at inotekcorp.com
- The PARP Link Homepage at parplink.u-strasbg.fr
- Poly+ADP+Ribose+Polymerase at the US National Library of Medicine Medical Subject Headings (MeSH)
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