ATP Binding to Rad5 Initiates Replication Fork Reversal by Inducing the Unwinding of the Leading Arm and the Formation of the Holliday Junction

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Replication fork reversal is one of the major pathways for reactivating stalled DNA replication. Many enzymes with replication fork reversal activity have DNA-unwinding activity as well, but none of the fork reversal enzymes in the SWI/SNF family shows a separate DNA-unwinding activity, raising the question of how they initiate the remodeling process. Here, we found ATP binding to Rad5 induces the unwinding of the leading arm of the replication fork and proximally positions the leading and lagging arms. This facilitates the spontaneous remodeling of the replication fork into a four-way junction. Once the four-way junction is formed, Rad5 migrates the four-way junction at a speed of 7.1 +/- 0.14 nt/s. The 3' end anchoring of the leading arm by Rad5's HIRAN domain is critical for both branch migration and the recovery of the three-way junction, but not for the structural transition to the four-way junction.
Publisher
CELL PRESS
Issue Date
2018-05
Language
English
Article Type
Article
Keywords

DNA-DAMAGE TOLERANCE; MAINTAINING GENOME STABILITY; TRANSLOCASE ACTIVITY; HIRAN DOMAIN; REGRESSION; RESTART; HLTF; INTEGRITY; HELICASE; SMARCAL1

Citation

CELL REPORTS, v.23, no.6, pp.1831 - 1839

ISSN
2211-1247
DOI
10.1016/j.celrep.2018.04.029
URI
http://hdl.handle.net/10203/242624
Appears in Collection
BS-Journal Papers(저널논문)
Files in This Item
2018 Hyun & Kim_Cell Reports.pdf(3.58 MB)Download
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