Regulation of Rad6/Rad18 Activity during DNA Damage Tolerance

Mark Hedglin, Stephen Benkovic

Research output: Contribution to journalArticle

39 Citations (Scopus)

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 Ubc13Mms2/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. ©

Original languageEnglish (US)
Pages (from-to)207-228
Number of pages22
JournalAnnual Review of Biophysics
Volume44
DOIs
StatePublished - Jun 22 2015

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Damage tolerance
DNA Damage
DNA
Proliferating Cell Nuclear Antigen
Ubiquitin
Polyubiquitin
DNA-Directed DNA Polymerase
Eukaryota
S Phase
Nucleotides
Clamping devices

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Bioengineering
  • Biochemistry
  • Cell Biology

Cite this

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Regulation of Rad6/Rad18 Activity during DNA Damage Tolerance. / Hedglin, Mark; Benkovic, Stephen.

In: Annual Review of Biophysics, Vol. 44, 22.06.2015, p. 207-228.

Research output: Contribution to journalArticle

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AU - Benkovic, Stephen

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