Reactome | PAR-PARP1,PAR-PARP2 dissociate from FEN1 and POLB

PAR-PARP1,PAR-PARP2 dissociate from FEN1 and POLB

Stable Identifier

R-HSA-5651739

Type

Reaction

Species

Homo sapiens

Compartment

nucleoplasm

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PAR-PARP1,PAR-PARP2 dissociate from FEN1 and POLB

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Auto-PARylated (poly(ADP-ribosylated)) PARP1 or PARP2 homodimers and heterodimers dissociate from DNA at single strand breaks (SSBs). The dissociation of PARP1 and/or PARP2 is necessary for completion of the long patch base excision repair (BER). In the presence of PARP inhibitors, PARP1 and/or PARP2 cannot auto-PARylate and remain bound to SSBs. This leads to persistence of SSBs, and generation of double strand breaks (DSBs) during DNA replication (Creissen and Shall 1982, Sukhanova et al. 2004, Sukhanova et al. 2005, Pachkowski et al. 2009, Heacock et al. 2010, Strom et al. 2011).

Literature References

PubMed ID	Title	Journal	Year
6278323	Regulation of DNA ligase activity by poly(ADP-ribose) Shall, S, Creissen, D	Nature	1982
15193131	Poly(ADP-ribose) polymerase-1 inhibits strand-displacement synthesis of DNA catalyzed by DNA polymerase beta Lavrik, OI, Khodyreva, SN, Sukhanova, MV	Biochemistry Mosc.	2004
15731342	Human base excision repair enzymes apurinic/apyrimidinic endonuclease1 (APE1), DNA polymerase beta and poly(ADP-ribose) polymerase 1: interplay between strand-displacement DNA synthesis and proofreading exonuclease activity Khodyreva, SN, Lavrik, OI, Sukhanova, MV, Lebedeva, NA, Wilson, SH, Prasad, R	Nucleic Acids Res.	2005
20573551	Alkylation DNA damage in combination with PARP inhibition results in formation of S-phase-dependent double-strand breaks Wilson, SH, Heacock, ML, Horton, JK, Stefanick, DF	DNA Repair (Amst.)	2010
19778542	Cells deficient in PARP-1 show an accelerated accumulation of DNA single strand breaks, but not AP sites, over the PARP-1-proficient cells exposed to MMS Tano, K, Nakamura, J, Takeda, S, Afonin, V, Watanabe, M, Swenberg, JA, Elder, RH, Pachkowski, BF	Mutat. Res.	2009
21183466	Poly (ADP-ribose) polymerase (PARP) is not involved in base excision repair but PARP inhibition traps a single-strand intermediate Szigyarto, CA, Helleday, T, Erixon, K, Uhlén, M, Ström, CE, Johansson, F	Nucleic Acids Res.	2011