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Cell Rep. 2014 Oct 23;9(2):460-8. doi: 10.1016/j.celrep.2014.09.005. Epub 2014 Oct 9.

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

Author information

1
Centro de Biología Molecular Severo Ochoa (CSIC/UAM), Cantoblanco, 28049 Madrid, Spain.
2
Centro de Biología Molecular Severo Ochoa (CSIC/UAM), Cantoblanco, 28049 Madrid, Spain. Electronic address: jatercero@cbm.csic.es.

Abstract

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 Rad5(HLTF/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.

PMID:
25310987
DOI:
10.1016/j.celrep.2014.09.005
[Indexed for MEDLINE]
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