PARP1,PARP2 dimers bound to MMEJ sites autoPARylate

Stable Identifier
Reaction [transition]
Homo sapiens
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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
25642963 Homologous-recombination-deficient tumours are dependent on Pol?-mediated repair

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

Nature 2015
20483915 The alternative end-joining pathway for repair of DNA double-strand breaks requires PARP1 but is not dependent upon microhomologies

Rhein, T, Mansour, WY, 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

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

J. Biol. Chem. 2001
8003475 Dual function for poly(ADP-ribose) synthesis in response to DNA strand breakage

Poirier, GG, Satoh, MS, Lindahl, T

Biochemistry 1994
Catalyst Activity

NAD+ ADP-ribosyltransferase activity of Extended microhomologous 3'-ssDNA overhangs-flap-DSB:MRN:RBBP8:PARP1,PARP2:FEN1:POLQ [nucleoplasm]

Orthologous Events
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