title: Characterization of human translesion DNA synthesis across a UV-induced DNA lesion.
abstract: Translesion DNA synthesis (TLS) during S-phase uses specialized TLS DNA polymerases to replicate a DNA lesion, allowing stringent DNA synthesis to resume beyond the offending damage. Human TLS involves the conjugation of ubiquitin to PCNA clamps encircling damaged DNA and the role of this post-translational modification is under scrutiny. A widely-accepted model purports that ubiquitinated PCNA recruits TLS polymerases such as pol η to sites of DNA damage where they may also displace a blocked replicative polymerase. We provide extensive quantitative evidence that the binding of pol η to PCNA and the ensuing TLS are both independent of PCNA ubiquitination. Rather, the unique properties of pols η and δ are attuned to promote an efficient and passive exchange of polymerases during TLS on the lagging strand.
authors: Department of Chemistry, The Pennsylvania State University, University Park, United States.
authors: Mark
authors: M
authors: Hedglin
authors: Department of Chemistry, The Pennsylvania State University, University Park, United States.
authors: Binod
authors: B
authors: Pandey
authors: Department of Chemistry, The Pennsylvania State University, University Park, United States.
authors: Stephen J
authors: 0000-0003-3680-3481
authors: SJ
authors: Benkovic
mesh_terms: D004247:DNA / Q000528:radiation effects*; D004260:DNA Repair; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D006801:Humans; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination; D014466:Ultraviolet Rays
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D025801:Ubiquitin; D004247:DNA; D004259:DNA-Directed DNA Polymerase
keywords: DNA damage tolerance; DNA polymerase delta; DNA polymerase eta; PCNA monoubiquitination; biochemistry; human; polymerase switching; translesion DNA Synthesis