The RecBC complex protects single-stranded DNA gaps during lesion bypass

• 成果类型: Article
• 署名作者: Philippin, Gaelle; Dupaigne, Pauline; Chrabaszcz, Elodie; Iturralde, Maialen; Modesti, Mauro; Le Cam, Eric; Pages, Vincent; Laureti, Luisa
• 署名单位: Aix-Marseille Universite; Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); UNICANCER; Institut Paoli-Calmette (IPC); Universite Paris Saclay; UNICANCER; Gustave Roussy; Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (Inserm); Aix-Marseille Universite; UNICANCER; Institut Paoli-Calmette (IPC)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10522
• DOI: 10.1073/pnas.2503839122
• 发表日期: 2025-09-16
• 关键词: escherichia-coli; homologous recombination; replication forks; leading-strand; exonuclease i; chi-asterisk; enzyme; repair; damage; ssb

摘要

Following encounter with an unrepaired DNA lesion, replication is halted and can restart downstream of the lesion leading to the formation of a single-stranded DNA (ssDNA) gap. To complete replication, this ssDNA gap is filled in by one of the two lesion tolerance pathways: the error-prone Translesion Synthesis (TLS) or the error-free Homology Directed Gap Repair (HDGR). In the present work, we evidence a role for the RecBC complex distinct from its canonical function in homologous recombination at DNA double strand breaks. We show that upon lesion encounter RecBC (independently of its catalytic activity and of the RecD subunit) is required to protect the nascent DNA in order to promote efficient lesion bypass. In the absence of RecBC, our data indicate that the nuclease ExoI can access and degrade the nascent DNA, affecting both TLS and HDGR mechanisms. We show that the recruitment of RecBC becomes particularly important at strong blocking lesions, when postreplicative ssDNA gaps persist and are covered by the ssDNA binding proteins. This protective role of RecBC is reminiscent of the role of BRCA2 in protecting the nascent DNA in human cells, highlighting once again the evolutionary conservation of DNA replication mechanisms across all living organisms.