Reactome | D-loop extension by DNA polymerases

D-loop extension by DNA polymerases

Stable Identifier

R-HSA-5693593

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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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