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  • 标题:Structure-specific DNA replication-fork recognition directs helicase and replication restart activities of the PriA helicase
  • 作者:Tricia A. Windgassen ; Maxime Leroux ; Kenneth A. Satyshur
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2018
  • 卷号:115
  • 期号:39
  • 页码:E9075-E9084
  • DOI:10.1073/pnas.1809842115
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:DNA replication restart, the essential process that reinitiates prematurely terminated genome replication reactions, relies on exquisitely specific recognition of abandoned DNA replication-fork structures. The PriA DNA helicase mediates this process in bacteria through mechanisms that remain poorly defined. We report the crystal structure of a PriA/replication-fork complex, which resolves leading-strand duplex DNA bound to the protein. Interaction with PriA unpairs one end of the DNA and sequesters the 3′-most nucleotide from the nascent leading strand into a conserved protein pocket. Cross-linking studies reveal a surface on the winged-helix domain of PriA that binds to parental duplex DNA. Deleting the winged-helix domain alters PriA’s structure-specific DNA unwinding properties and impairs its activity in vivo. Our observations lead to a model in which coordinated parental-, leading-, and lagging-strand DNA binding provide PriA with the structural specificity needed to act on abandoned DNA replication forks.
  • 关键词:DNA replication restart ; DNA repair ; X-ray crystallography ; protein–DNA complex ; cross-link mapping
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