PARP1,PARP2 dimers bound to MMEJ sites autoPARylate

Stable Identifier
R-HSA-5687653
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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PARP inihibitors that block catalytic activity of PARP1 (or PARP2) bound to single-stranded DNA (ssDNA), including PARP1 and PARP2 autoPARylation (auto-polyADPribosylation), also inhibit microhomology-mediated end joining (MMEJ). Thus, the catalytic activity of PARP1 (or PARP2), related to autoPARylation or PARylation of other proteins at MMEJ site, is necessary for the progression of MMEJ (Mansour et al. 2010, Ceccaldi et al. 2015). By analogy with the DNA polymerase beta (POLB)-dependent long patch base excision repair (Satoh et al. 1994, Prasad et al. 2001), autoPARylated PARPs dissociate from the repair site, thereby coordinating the termination of strand displacement DNA synthesis and the cleavage of displaced strand flaps by FEN1.

Literature References
PubMed ID Title Journal Year
20483915 The alternative end-joining pathway for repair of DNA double-strand breaks requires PARP1 but is not dependent upon microhomologies

Mansour, WY, Rhein, T, Dahm-Daphi, J

Nucleic Acids Res. 2010
11440997 DNA polymerase beta -mediated long patch base excision repair. Poly(ADP-ribose)polymerase-1 stimulates strand displacement DNA synthesis

Prasad, R, Lavrik, OI, Kim, SJ, Kedar, P, Yang, XP, Vande Berg, BJ, Wilson, SH

J. Biol. Chem. 2001
25642963 Homologous-recombination-deficient tumours are dependent on Pol?-mediated repair

Ceccaldi, R, Liu, JC, Amunugama, R, Hajdu, I, Primack, B, Petalcorin, MI, O'Connor, KW, Konstantinopoulos, PA, Elledge, SJ, Boulton, SJ, Yusufzai, T, D'Andrea, AD

Nature 2015
8003475 Dual function for poly(ADP-ribose) synthesis in response to DNA strand breakage

Satoh, MS, Poirier, GG, Lindahl, T

Biochemistry 1994
Participants
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Catalyst Activity
Catalyst Activity
Title
NAD+ ADP-ribosyltransferase activity of Extended microhomologous 3'-ssDNA overhangs-flap-DSB:MRN:RBBP8:PARP1,PARP2:FEN1:POLQ [nucleoplasm]
Physical Entity
Activity
Orthologous Events
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