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Title

Rad5 plays a major role in the cellular response to DNA damage during chromosome replication

AuthorsOrtiz-Bazán, María Ángeles ; Gallo-Fernández, María ; Saugar, Irene ; Jiménez-Martín, Alberto; Vázquez, María Victoria ; Tercero, José Antonio
Issue Date9-Oct-2014
PublisherCell Press
CitationCell Reports 9: 460- 468 (2014)
Abstract© 2014 The Authors. The RAD6/RAD18 pathway of DNA damage tolerance overcomes unrepaired lesions that block replication forks. It is subdivided into two branches: translesion DNA synthesis, which is frequently error prone, and the error-free DNA-damage-avoidance subpathway. Here, we show that Rad5HLTF/SHPRH, which mediates the error-free branch, has a major role in the response to DNA damage caused by methyl methanesulfonate (MMS) during chromosome replication, whereas translesion synthesis polymerases make only a minor contribution. Both the ubiquitin-ligase and the ATPase/helicase activities of Rad5 are necessary for this cellular response. We show that Rad5 is required for the progression of replication forks through MMS-damaged DNA. Moreover, supporting its role during replication, this protein reaches maximum levels during S phase and forms subnuclear foci when replication occurs in the presence of DNA damage. Thus, Rad5 ensures the completion of chromosome replication under DNA-damaging conditions while minimizing the risk of mutagenesis, thereby contributing significantly to genome integrity maintenance.
URIhttp://hdl.handle.net/10261/125357
DOI10.1016/j.celrep.2014.09.005
Identifiersdoi: 10.1016/j.celrep.2014.09.005
issn: 2211-1247
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