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Título: | Rad5 plays a major role in the cellular response to DNA damage during chromosome replication |
Autor: | Ortiz-Bazán, María Ángeles CSIC; Gallo-Fernández, María CSIC; Saugar, Irene; Jiménez-Martín, Alberto CSIC ORCID; Vázquez, María Victoria CSIC; Tercero, José Antonio CSIC ORCID | Fecha de publicación: | 9-oct-2014 | Editor: | Cell Press | Citación: | Cell Reports 9: 460- 468 (2014) | Resumen: | © 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. | URI: | http://hdl.handle.net/10261/125357 | DOI: | 10.1016/j.celrep.2014.09.005 | Identificadores: | doi: 10.1016/j.celrep.2014.09.005 issn: 2211-1247 |
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TerceroJ_Rad5PlaysaMajorRoleintheCellularResponse.pdf | 2,94 MB | Adobe PDF | Visualizar/Abrir |
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