Characterization of human translesion DNA synthesis across a UV-induced DNA lesion

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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.

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Mark Hedglin

Department of Chemistry, The Pennsylvania State University, University Park, United States

Competing interests
The authors declare that no competing interests exist.
Binod Pandey

Department of Chemistry, The Pennsylvania State University, University Park, United States

Competing interests
The authors declare that no competing interests exist.
Stephen J Benkovic

Department of Chemistry, The Pennsylvania State University, University Park, United States

For correspondence
sjb1@psu.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-3680-3481

Funding

National Institutes of Health (GM13306)

Stephen J Benkovic

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.