https://scholars.lib.ntu.edu.tw/handle/123456789/378518
標題: | Pif1 helicase and Polδ promote recombination-coupled DNA synthesis via bubble migration | 作者: | Wilson, Marenda A. Kwon, Youngho Xu, Yuanyuan Chung, Woo-Hyun HUNG-YUAN CHI Niu, Hengyao Mayle, Ryan Chen, Xuefeng Malkova, Anna Sung, Patrick Ira, Grzegorz |
公開日期: | 2013 | 卷: | 502 | 期: | 7471 | 起(迄)頁: | 393 - 396 | 來源出版物: | Nature | 摘要: | During DNA repair by homologous recombination (HR), DNA synthesis copies information from a template DNA molecule. Multiple DNA polymerases have been implicated in repair-specific DNA synthesis, but it has remained unclear whether a DNA helicase is involved in this reaction. A good candidate DNA helicase is Pif1, an evolutionarily conserved helicase in Saccharomyces cerevisiae important for break-induced replication (BIR) as well as HR-dependent telomere maintenance in the absence of telomerase found in 10-15% of all cancers. Pif1 has a role in DNA synthesis across hard-to-replicate sites and in lagging-strand synthesis with polymerase δ (Polδ). Here we provide evidence that Pif1 stimulates DNA synthesis during BIR and crossover recombination. The initial steps of BIR occur normally in Pif1-deficient cells, but Polδ recruitment and DNA synthesis are decreased, resulting in premature resolution of DNA intermediates into half-crossovers. Purified Pif1 protein strongly stimulates Polδ-mediated DNA synthesis from a D-loop made by the Rad51 recombinase. Notably, Pif1 liberates the newly synthesized strand to prevent the accumulation of topological constraint and to facilitate extensive DNA synthesis via the establishment of a migrating D-loop structure. Our results uncover a novel function of Pif1 and provide insights into the mechanism of HR. ? 2013 Macmillan Publishers Limited. All rights reserved. |
URI: | http://www.scopus.com/inward/record.url?eid=2-s2.0-84885866032&partnerID=MN8TOARS http://scholars.lib.ntu.edu.tw/handle/123456789/378518 |
ISSN: | 14764687 | DOI: | 10.1038/nature12585 | SDG/關鍵字: | BIR protein; DNA; DNA directed DNA polymerase delta; helicase; Pif1 helicase; Rad51 protein; unclassified drug; unclassified enzyme; cancer; enzyme activity; mitochondrial DNA; polymerase chain reaction; protein; recombination; topology; yeast; animal cell; article; cell function; cell migration; chromatin immunoprecipitation; controlled study; DNA repair; DNA structure; DNA synthesis; fungal strain; homologous recombination; nonhuman; polymerase chain reaction; priority journal; protein expression; protein function; protein localization; Saccharomyces cerevisiae; Crossing Over, Genetic; DNA Helicases; DNA Polymerase III; DNA Repair; DNA Replication; DNA, Fungal; Nucleic Acid Conformation; Rad51 Recombinase; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Saccharomyces cerevisiae |
顯示於: | 生化科學研究所 |
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