D-loop extension by DNA polymerases

Stable Identifier
Reaction [transition]
Homo sapiens
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Following branch migration, the invading 3' resected ssDNA end of the double-strand break (DSB) acts as a primer for repair DNA synthesis using the complementary strand of the invaded duplex as a template. The replicative DNA polymerases delta (POLD) and likely epsilon (POLE), as well as translesion synthesis (TLS) DNA polymerases eta (POLH) and kappa (POLK) in complex with PCNA, RFC and RPA are implicated in DNA repair synthesis and D-loop extension. While TLS polymerases increase the efficiency of homologous recombination-related DNA synthesis and can directly interact with D-loop proteins RAD51, PALB2 and BRCA2, it is likely that replicative DNA polymerases POLD and POLE, with their high processivity and fidelity, perform the major role in D-loop extension (McIlwraith et al. 2005, Sebesta et al. 2013, Pomerantz et al. 2013, Buisson et al. 2014). In addition, the presence of RAD51-translocases, homologous to yeast Rad54, that remove RAD51 from the 3' invading strand, may be necessary for the catalytic activity of POLD or POLE (Li et al. 2009, Li and Heyer 2009).
Literature References
PubMed ID Title Journal Year
23686288 Preferential D-loop extension by a translesion DNA polymerase underlies error-prone recombination

Goodman, MF, O'Donnell, ME, Kurth, I, Pomerantz, RT

Nat. Struct. Mol. Biol. 2013
11006276 Fidelity and processivity of DNA synthesis by DNA polymerase kappa, the product of the human DINB1 gene

Gerlach, VL, Feaver, WJ, Friedberg, EC, Kunkel, TA, Matsuda, T, Ohashi, E, Bebenek, K, Ohmori, H

J. Biol. Chem. 2000
15916957 Trading places: how do DNA polymerases switch during translesion DNA synthesis?

Friedberg, EC, Lehmann, AR, Fuchs, RP

Mol. Cell 2005
23731732 Role of PCNA and TLS polymerases in D-loop extension during homologous recombination in humans

Haracska, L, Szabo, JE, Burkovics, P, Zhang, S, Sebesta, M, Krejci, L, Lee, MY, Juhasz, S

DNA Repair (Amst.) 2013
16337601 Human DNA polymerase eta promotes DNA synthesis from strand invasion intermediates of homologous recombination

West, SC, Vaisman, A, Mcllwraith, MJ, McIlwraith, MJ, Woodgate, R, Fanning, E, Liu, Y

Mol. Cell 2005
10856253 Mechanisms of accurate translesion synthesis by human DNA polymerase eta.

Kusumoto, R, Iwai, S, Masutani, C, Hanaoka, F

EMBO J 2000
19941829 PCNA is required for initiation of recombination-associated DNA synthesis by DNA polymerase delta

Heyer, WD, Li, X, Burgers, PM, Stith, CM

Mol. Cell 2009
10801132 Low fidelity DNA synthesis by human DNA polymerase-eta

Kunkel, TA, Masutani, C, Matsuda, T, Bebenek, K, Hanaoka, F

Nature 2000
24485656 Breast cancer proteins PALB2 and BRCA2 stimulate polymerase ? in recombination-associated DNA synthesis at blocked replication forks

Zhao, W, Masson, JY, Coulombe, Y, Pauty, J, Niraj, J, Maity, R, Buisson, R, Sung, P

Cell Rep 2014
19074197 RAD54 controls access to the invading 3'-OH end after RAD51-mediated DNA strand invasion in homologous recombination in Saccharomyces cerevisiae

Heyer, WD, Li, X

Nucleic Acids Res. 2009
Event Information
Catalyst Activity

DNA-directed DNA polymerase activity of PCNA:POLD,POLE,POLH,POLK:RPA:RFC [nucleoplasm]

Orthologous Events
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