Role of DNA damage-induced replication checkpoint in promoting lesion bypass by translesion synthesis in yeast

Vincent Pagès, Sergio R. Santa Maria, Louise Prakash, Satya Prakash

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Unrepaired DNA lesions in the template strand block the replication fork. In yeast, Mec1 protein kinase-mediated replication checkpoint prevents the breakdown of replication forks and maintains viability in DNA-damaged cells going through the S phase. By ensuring that the replisome does not dissociate from the fork stalled at the lesion site, the replication checkpoint presumably coordinates the action of lesion bypass processes with the replisome. However, it has remained unclear as to which of the lesion bypass processes - translesion synthesis (TLS) and/or template switching - depend on the activation of the replication checkpoint. Here we determine if the Mec1 kinase and the subunits of the checkpoint clamp and the clamp loader are required for TLS. We show that proficient TLS can occur in the absence of these checkpoint proteins in nucleotide excision repair (NER)-proficient cells; however, in the absence of NER, checkpoint protein-mediated Rev1 phosphorylation contributes to increasing the proficiency of DNA polymerase ζ-dependent TLS.

Original languageEnglish (US)
Pages (from-to)1438-1449
Number of pages12
JournalGenes and Development
Volume23
Issue number12
DOIs
StatePublished - Jun 15 2009

Fingerprint

DNA Repair
DNA Damage
Yeasts
DNA
DNA-Directed DNA Polymerase
S Phase
Protein Kinases
Proteins
Phosphotransferases
Phosphorylation

Keywords

  • DNA damage
  • Lesion bypass
  • Mec1 kinase Rev1 phosphorylation
  • Replication checkpoint
  • Translesion synthesis

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology
  • Medicine(all)

Cite this

Role of DNA damage-induced replication checkpoint in promoting lesion bypass by translesion synthesis in yeast. / Pagès, Vincent; Santa Maria, Sergio R.; Prakash, Louise; Prakash, Satya.

In: Genes and Development, Vol. 23, No. 12, 15.06.2009, p. 1438-1449.

Research output: Contribution to journalArticle

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