title: Monoubiquitylation of histone H2B contributes to the bypass of DNA damage during and after DNA replication.
abstract: DNA lesion bypass is mediated by DNA damage tolerance (DDT) pathways and homologous recombination (HR). The DDT pathways, which involve translesion synthesis and template switching (TS), are activated by the ubiquitylation (ub) of PCNA through components of theRAD6-RAD18pathway, whereas the HR pathway is independent ofRAD18However, it is unclear how these processes are coordinated within the context of chromatin. Here we show that Bre1, an ubiquitin ligase specific for histone H2B, is recruited to chromatin in a manner coupled to replication of damaged DNA. In the absence of Bre1 or H2Bub, cells exhibit accumulation of unrepaired DNA lesions. Consequently, the damaged forks become unstable and resistant to repair. We provide physical, genetic, and cytological evidence that H2Bub contributes toward both Rad18-dependent TS and replication fork repair by HR. Using an inducible system of DNA damage bypass, we further show that H2Bub is required for the regulation of DDT after genome duplication. We propose that Bre1-H2Bub facilitates fork recovery and gap-filling repair by controlling chromatin dynamics in response to replicative DNA damage.
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Nankang, Taipei 11529, Taiwan.|Graduate Institute of Life Sciences, National Defence Medical Center, Neihu, Taipei 11490, Taiwan.
authors.forename: Shih-Hsun
authors.initials: SH
authors.lastname: Hung
authors.affiliation: Institute of Molecular Biology, 55128 Mainz, Germany.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Wong
authors.affiliation: Institute of Molecular Biology, 55128 Mainz, Germany ckao@gate.sinica.edu.tw h.ulrich@imb-mainz.de.
authors.forename: Helle D
authors.initials: HD
authors.lastname: Ulrich
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Nankang, Taipei 11529, Taiwan; ckao@gate.sinica.edu.tw h.ulrich@imb-mainz.de.|Graduate Institute of Life Sciences, National Defence Medical Center, Neihu, Taipei 11490, Taiwan.
authors.forename: Cheng-Fu
authors.initials: CF
authors.lastname: Kao
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair; D004261:DNA Replication; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D059765:Homologous Recombination; D051135:Rad51 Recombinase / Q000378:metabolism; D018741:Replication Origin; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D000477:Alkylating Agents; D002843:Chromatin; D005656:Fungal Proteins; D006657:Histones; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D051135:Rad51 Recombinase
keywords: Bre1 E3 ubiquitin ligase; DNA damage tolerance; H2B ubiquitylation; chromatin; homologous recombination