title: Regulation of Rad6/Rad18 Activity During DNA Damage Tolerance.
abstract: Replicative polymerases (pols) cannot accommodate damaged template bases, and these pols stall when such offenses are encountered during S phase. Rather than repairing the damaged base, replication past it may proceed via one of two DNA damage tolerance (DDT) pathways, allowing replicative DNA synthesis to resume. In translesion DNA synthesis (TLS), a specialized TLS pol is recruited to catalyze stable, yet often erroneous, nucleotide incorporation opposite damaged template bases. In template switching, the newly synthesized sister strand is used as a damage-free template to synthesize past the lesion. In eukaryotes, both pathways are regulated by the conjugation of ubiquitin to the PCNA sliding clamp by distinct E2/E3 pairs. Whereas monoubiquitination by Rad6/Rad18 mediates TLS, extension of this ubiquitin to a polyubiquitin chain by Ubc13-Mms2/Rad5 routes DDT to the template switching pathway. In this review, we focus on the monoubiquitination of PCNA by Rad6/Rad18 and summarize the current knowledge of how this process is regulated.
authors.affiliation: Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802; email: muh218@psu.edu , sjb1@psu.edu.
authors.forename: Mark
authors.initials: M
authors.lastname: Hedglin
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Benkovic
mesh_terms: D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D004268:DNA-Binding Proteins; D018809:Proliferating Cell Nuclear Antigen; D025801:Ubiquitin; D044763:Ubiquitin-Conjugating Enzymes
keywords: DNA damage; DNA damage tolerance; PCNA; Rad6/Rad18; ubiquitin