title: Rad5 plays a major role in the cellular response to DNA damage during chromosome replication.
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.
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC/UAM), Cantoblanco, 28049 Madrid, Spain.
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: Ortiz-Bazán
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC/UAM), Cantoblanco, 28049 Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Gallo-Fernández
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC/UAM), Cantoblanco, 28049 Madrid, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Saugar
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC/UAM), Cantoblanco, 28049 Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Jiménez-Martín
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC/UAM), Cantoblanco, 28049 Madrid, Spain.
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Vázquez
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC/UAM), Cantoblanco, 28049 Madrid, Spain. Electronic address: jatercero@cbm.csic.es.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Tercero
mesh_terms: D015825:Chromosomes, Fungal / Q000235:genetics*; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D008741:Methyl Methanesulfonate / Q000633:toxicity; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D008741:Methyl Methanesulfonate; C076225:RAD5 protein, S cerevisiae; D004265:DNA Helicases