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Structure-specific DNA replication-fork recognition directs helicase and replication restart activities of the PriA helicase

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [1];  [2];  [1];  [2];  [1]
  1. Univ. of Wisconsin School of Medicine and Public Health, Madison, WI (United States)
  2. Univ. of Massachusetts, Amherst, MA (United States)
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. Here, 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.
Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
National Inst. of Health; National Science Foundation
OSTI ID:
1477117
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 39 Vol. 115; ISSN 0027-8424
Publisher:
National Academy of SciencesCopyright Statement
Country of Publication:
United States
Language:
ENGLISH

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Cited By (4)

A new role for Escherichia coli Dam DNA methylase in prevention of aberrant chromosomal replication journal April 2019
Omnipresent Maxwell's demons orchestrate information management in living cells journal February 2019
Use of 6‐Methylisoxanthopterin, a Fluorescent Guanine Analog, to Probe Fob1‐Mediated Dynamics at the Stalling Fork Barrier DNA Sequences journal October 2019
Function of a strand-separation pin element in the PriA DNA replication restart helicase journal December 2018

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