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

Stable Identifier
R-HSA-5651739
Type
Reaction [dissociation]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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
15193131 Poly(ADP-ribose) polymerase-1 inhibits strand-displacement synthesis of DNA catalyzed by DNA polymerase beta

Sukhanova, MV, Khodyreva, SN, Lavrik, OI

Biochemistry Mosc. 2004
6278323 Regulation of DNA ligase activity by poly(ADP-ribose)

Creissen, D, Shall, S

Nature 1982
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

Sukhanova, MV, Khodyreva, SN, Lebedeva, NA, Prasad, R, Wilson, SH, Lavrik, OI

Nucleic Acids Res. 2005
20573551 Alkylation DNA damage in combination with PARP inhibition results in formation of S-phase-dependent double-strand breaks

Heacock, ML, Stefanick, DF, Horton, JK, Wilson, SH

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

Pachkowski, BF, Tano, K, Afonin, V, Elder, RH, Takeda, S, Watanabe, M, Swenberg, JA, Nakamura, J

Mutat. Res. 2009
21183466 Poly (ADP-ribose) polymerase (PARP) is not involved in base excision repair but PARP inhibition traps a single-strand intermediate

Ström, CE, Johansson, F, Uhlén, M, Szigyarto, CA, Erixon, K, Helleday, T

Nucleic Acids Res. 2011
Participants
Participant Of
Orthologous Events
Authored
Reviewed
Created