FANCD2-dependent mitotic DNA synthesis relies on PCNA K164 ubiquitination.

ABSTRACT: Ubiquitination of proliferating cell nuclear antigen (PCNA) at lysine 164 (K164) activates DNA damage tolerance pathways. Currently, we lack a comprehensive understanding of how PCNA K164 ubiquitination promotes genome stability. To evaluate this, we generated stable cell lines expressing PCNA^K164R from the endogenous PCNA locus. Our data reveal that the inability to ubiquitinate K164 causes perturbations in global DNA replication. Persistent replication stress generates under-replicated regions and is exacerbated by the DNA polymerase inhibitor aphidicolin. We show that these phenotypes are due, in part, to impaired Fanconi anemia group D2 protein (FANCD2)-dependent mitotic DNA synthesis (MiDAS) in PCNA^K164R cells. FANCD2 mono-ubiquitination is significantly reduced

SUBMITTER: Leung W 

PROVIDER: S-EPMC10842461 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature