PARP1 or PARP2, FEN1 and POLQ are recruited to MMEJ site

Stable Identifier
R-HSA-5687484
Type
Reaction [binding]
Species
Homo sapiens
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Flap endonuclease FEN1, DNA polymerase theta (POLQ) and PARP1 or PARP2 homo- or heterodimers are recruited to DNA double strand breaks (DSBs) resected by MRN and RBBP8 (CtIP) in the process of microhomology-mediated end joining (MMEJ). The mechanism of recruitment of FEN1, PARP1 (or PARP2) and POLQ, which are all necessary for MMEJ progression (Liang et al. 2005, Mansour et al. 2010, Sharma et al. 2015, Mateos-Gomez et al. 2015, Ceccaldi et al. 2015, Kent et al. 2015), is poorly defined. PARP1 (or PARP2) recognizes ssDNA. In the DNA polymerase beta (POLB)-dependent long patch base excision repair (BER), PARPs form ternary complexes with FEN1 and POLB (Prasad et al. 2001, Lavrik et al. 2001, Cistulli et al. 2004), and it is possible that a similar mechanism involving PARPs, FEN1 and POLQ operates in MMEJ. POLQ functions as a homodimer and facilitates annealing of two 3'-ssDNA overhangs through their microhomology regions. POLQ requires <20 nucleotide (nt) long resected overhangs (Kent et al. 2015). Microhomology regions are optimally 10-19 nt long (Sharma et al. 2015), and the annealing is facilitated if the microhomology region is GC-rich (Kent et al. 2015).

Literature References
PubMed ID Title Journal Year
25789972 Homology and enzymatic requirements of microhomology-dependent alternative end joining

Sharma, S, Javadekar, SM, Pandey, M, Srivastava, M, Kumari, R, Raghavan, SC

Cell Death Dis 2015
16012167 Modulation of DNA end joining by nuclear proteins

Liang, L, Deng, L, Chen, Y, Li, GC, Shao, C, Tischfield, JA

J. Biol. Chem. 2005
25643323 Mechanism of microhomology-mediated end-joining promoted by human DNA polymerase ?

Kent, T, Chandramouly, G, McDevitt, SM, Ozdemir, AY, Pomerantz, RT

Nat. Struct. Mol. Biol. 2015
11340072 Photoaffinity labeling of mouse fibroblast enzymes by a base excision repair intermediate. Evidence for the role of poly(ADP-ribose) polymerase-1 in DNA repair

Lavrik, OI, Prasad, R, Sobol, RW, Horton, JK, Ackerman, EJ, Wilson, SH

J. Biol. Chem. 2001
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
25642960 Mammalian polymerase ? promotes alternative NHEJ and suppresses recombination

Mateos-Gomez, PA, Gong, F, Nair, N, Miller, KM, Lazzerini-Denchi, E, Sfeir, A

Nature 2015
15135726 AP endonuclease and poly(ADP-ribose) polymerase-1 interact with the same base excision repair intermediate

Cistulli, C, Lavrik, OI, Prasad, R, Hou, E, Wilson, SH

DNA Repair (Amst.) 2004
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
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
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