Poly ADP ribose polymerase

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Poly (ADP-ribose) polymerase (PARP) is a protein involved in a number of cellular processes involving mainly DNA repair and programmed cell death.

Contents 1 Members of PARP family 2 Functions 2.1 Role in forming polymer of ADP-ribose (PAR) 2.2 Role in repairing DNA nicks 2.3 Role of tankyrases 3 External links

[edit] 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) have a confirmed PARP activity.

• Others include PARP6, TIPARP (or "PARP7"), PARP8, PARP9,PARP10, PARP11, PARP12, PARP14, PARP15, and PARP16.

[edit] Functions

[edit] Role in forming polymer of ADP-ribose (PAR)

These enzymes have the capacity to make a polymer of ADP-ribose (PAR) from NAD (nicotinamide adenine dinucleotide).

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).

[edit] 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.

[edit] 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 trafficking 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.

[edit] External links

• 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
• MeSH Poly+ADP+Ribose+Polymerase

v • d • e Transferases: glycosyltransferases (EC 2.4) 2.4.1 - Hexosyltransferases: glucosyltransferase Phosphorylase (Starch, Glycogen, Myo-) - Glycogen synthase - Debranching enzyme - Branching enzyme - 1,3-beta-glucan synthase - Ceramide glucosyltransferase 2.4.1 - Hexosyltransferases: other Galactosyltransferase (Lactose synthase, B-N-acetylglucosaminyl-glycopeptide b-1,4-galactosyltransferase) Glucuronosyltransferase (UGT1A1, UGT2B7, Hyaluronan synthase) Fucosyltransferase (POFUT1, POFUT2) 2.4.2 - Pentosyltransferases: ADP ribose Cholera toxin - Diphtheria toxin - Pertussis toxin - Poly ADP ribose polymerase 2.4.2 - Pentosyltransferases: other Purine nucleoside phosphorylase - Adenine phosphoribosyltransferase - Hypoxanthine-guanine phosphoribosyltransferase - Uracil phosphoribosyltransferase - Amidophosphoribosyltransferase - Xylosyltransferase