Pif1 helicase and Polδ promote recombination-coupled DNA synthesis via bubble migration

作者: Marenda A. Wilson , YoungHo Kwon , Yuanyuan Xu , Woo-Hyun Chung , Peter Chi

DOI: 10.1038/NATURE12585

关键词: DNA replicationGeneticsControl of chromosome duplicationDNA clampPrimaseDNA polymeraseReplication protein ABiologyDNA polymerase IIEukaryotic DNA replication

摘要: This paper demonstrates that Pif1 helicase works with polymerase d to promote DNA synthesis through a migrating D-loop, mechanism used copy tens of kilobases during repair chromosome breaks by break-induced replication (BIR). When is repaired homologous recombination, involved in the latter stages. Two papers published this issue Nature now define role for reaction. They show although initial stages (BIR) can occur normally absence Pif1, from D-loop intermediate compromised. The BIR involves unique bubble-like fork results conservative inheritance new genetic material, contrast S-phase duplicates genome before cell division, and inherently mutagenic. During recombination (HR), copies information template molecule. Multiple polymerases have been implicated repair-specific synthesis1,2,3, but it has remained unclear whether A good candidate an evolutionarily conserved Saccharomyces cerevisiae important (BIR)4 as well HR-dependent telomere maintenance telomerase5 found 10–15% all cancers6. across hard-to-replicate sites7,8 lagging-strand δ (Polδ)9,10,11. Here we provide evidence stimulates crossover recombination. steps Pif1-deficient cells, Polδ recruitment are decreased, resulting premature resolution intermediates into half-crossovers. Purified protein strongly Polδ-mediated made Rad51 recombinase. Notably, liberates newly synthesized strand prevent accumulation topological constraint facilitate extensive via establishment structure. Our uncover novel function insights HR.

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