Damage-specific modification of PCNA

Research output: Contribution to journalReview articlepeer-review

11 Scopus citations

Abstract

Okazaki fragment processing is an integral part of DNA replication. For a long time, we assumed that the maturation of these small RNA-primed DNA fragments did not necessarily have to occur during S phase, but could be postponed to late in S phase after the bulk of DNA synthesis had been completed. This view was primarily based on the arrest phenotype of temperature-sensitive DNA ligase I mutants in yeast, which accumulated with an almost fully duplicated set of chromosomes. However, many temperature-sensitive alleles can be leaky and the re-evaluation of DNA ligase I-deficient cells has offered new and unexpected insights into how cells keep track of lagging strand synthesis. It turns out that if Okazaki fragment joining goes awry, cells have their own alarm system in the form of ubiquitin that is conjugated to the replication clamp PCNA. Although this modification results in mono- and poly-ubiquitination of PCNA, it is genetically distinct from the known post-replicative repair mark at lysine 164. In this Extra View, we discuss the possibility that eukaryotic cells utilize different enzymatic pathways and ubiquitin attachment sites on PCNA to alert the replication machinery to the accumulation of single-stranded gaps or nicks behind the fork.

Original languageEnglish (US)
Pages (from-to)3698-3703
Number of pages6
JournalCell Cycle
Volume9
Issue number18
DOIs
StatePublished - Sep 15 2010

Bibliographical note

Funding Information:
We thank Dr. Xiaolan Zhao for the anti-SUMO antibody and Dr. Eric A. Hendrickson for reading the manu script. We acknowledge the assistance of the Flow Cytometry Core Facility at the University of Minnesota. Molecular graphics images were produced using the UCSF Chimera package from the Resource for Biocomputing, Visualization and Informatics at the University of California, San Francisco (supported by NIH P41 RR-01081). This work was supported by NIH grant GM074917 to A.K.B., who is a Scholar of the Leukemia and Lymphoma Society.

Keywords

  • DNA ligase I
  • DNA replication
  • Okazaki fragment processing
  • PCNA
  • SUMO
  • Ubiquitin

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