Gap-filling DNA synthesis in SDSA

Stable Identifier
R-HSA-5693558
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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After synthesis-dependent strand annealing (SDSA), the reannealed DNA molecule contains a single strand nick (SSB) in the newly synthesized strand, between the 3' end of the newly added stretch of nucleotides and the resected 5' end of the strand. In addition, the complementary strand contains a gap created by resection that was not filled during DNA repair synthesis. Additional DNA synthesis occurs to fill in this remaining single-strand gap present in the reannealed DNA duplex. SSBs between newly added stretches of nucleotides and resected 5' ends need to be closed by DNA ligases. The identity of DNA polymerase(s) and DNA ligase(s) involved in the completion of DNA double-strand break repair through SDSA is not known. RTEL1 DNA helicase, which resolves D-loops in SDSA, binds PCNA and may promote DNA synthesis after reannealing (Vannier et al. 2013). DNA polymerase alpha is implicated in late steps of DNA repair synthesis (Levy et al. 2009), but other PCNA-bound DNA polymerases may also be involved. LIG1, as well as LIG3 in complex with XRCC1, may act to ligate SSBs (Fan et al. 2004, Mortusewicz et al. 2006, Mortusewicz et al. 2007, Puebla-Osorio et al. 2006).
Literature References
PubMed ID Title Journal Year
17880707 XRCC1 and PCNA are loading platforms with distinct kinetic properties and different capacities to respond to multiple DNA lesions

Mortusewicz, O, Leonhardt, H

BMC Mol. Biol. 2007
24115439 RTEL1 is a replisome-associated helicase that promotes telomere and genome-wide replication

Ding, H, Petalcorin, MI, Sandhu, S, Boulton, SJ, Wu, X, Vannier, JB, Nabi, Z

Science 2013
16648486 Early embryonic lethality due to targeted inactivation of DNA ligase III

Zhu, C, Alt, FW, Puebla-Osorio, N, Lacey, DB

Mol. Cell. Biol. 2006
15107487 XRCC1 co-localizes and physically interacts with PCNA

Otterlei, M, Wilson, DM, Fan, J, Wong, HK, Tomkinson, AE

Nucleic Acids Res. 2004
19305001 XRCC1 interacts with the p58 subunit of DNA Pol alpha-primase and may coordinate DNA repair and replication during S phase

Bresson, A, Maiorano, D, de Murcia, G, Van Dorsselaer, A, Oehlmann, M, Ménissier-de Murcia, J, Schreiber, V, Delalande, F, Nasheuer, HP, Lévy, N

Nucleic Acids Res. 2009
16855289 Differential recruitment of DNA Ligase I and III to DNA repair sites

Rothbauer, U, Mortusewicz, O, Leonhardt, H, Cardoso, MC

Nucleic Acids Res. 2006
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