Reactome | PARP1,PARP2 dimers bound to MMEJ sites autoPARylate

PARP1,PARP2 dimers bound to MMEJ sites autoPARylate

Stable Identifier

R-HSA-5687653

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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PARP1,PARP2 dimers bound to MMEJ sites autoPARylate

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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
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
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
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
8003475	Dual function for poly(ADP-ribose) synthesis in response to DNA strand breakage Poirier, GG, Satoh, MS, Lindahl, T	Biochemistry	1994

Participants

Input

Output

Participates

as an event of

HDR through MMEJ (alt-NHEJ) (Homo sapiens)

Catalyst Activity

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

Physical Entity

Extended microhomologous 3'-ssDNA overhangs-flap-DSB:MRN:RBBP8:PARP1,PARP2:FEN1:POLQ [nucleoplasm] (Homo sapiens)

Activity

NAD+-protein poly-ADP-ribosyltransferase activity (GO:0003950)

Orthologous Events

PARP1,PARP2 dimers bound to MMEJ sites autoPARylate (Bos taurus)

PARP1,PARP2 dimers bound to MMEJ sites autoPARylate (Drosophila melanogaster)

PARP1,PARP2 dimers bound to MMEJ sites autoPARylate (Gallus gallus)

PARP1,PARP2 dimers bound to MMEJ sites autoPARylate (Mus musculus)

PARP1,PARP2 dimers bound to MMEJ sites autoPARylate (Rattus norvegicus)

PARP1,PARP2 dimers bound to MMEJ sites autoPARylate (Sus scrofa)

Authored