Spatial separation between replisome- and template-induced replication stress signaling

Néstor García-Rodríguez, Magdalena Morawska, Ronald P. Wong, Yasukazu Daigaku, Helle D. Ulrich

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

Polymerase-blocking DNA lesions are thought to elicit a checkpoint response via accumulation of single-stranded DNA at stalled replication forks. However, as an alternative to persistent fork stalling, re-priming downstream of lesions can give rise to daughter-strand gaps behind replication forks. We show here that the processing of such structures by an exonuclease, Exo1, is required for timely checkpoint activation, which in turn prevents further gap erosion in S phase. This Rad9-dependent mechanism of damage signaling is distinct from the Mrc1-dependent, fork-associated response to replication stress induced by conditions such as nucleotide depletion or replisome-inherent problems, but reminiscent of replication-independent checkpoint activation by single-stranded DNA. Our results indicate that while replisome stalling triggers a checkpoint response directly at the stalled replication fork, the response to replication stress elicited by polymerase-blocking lesions mainly emanates from Exo1-processed, postreplicative daughter-strand gaps, thus offering a mechanistic explanation for the dichotomy between replisome- versus template-induced checkpoint signaling.

Original languageEnglish
Article numbere98369
JournalEMBO Journal
Volume37
Issue number9
DOIs
Publication statusPublished - 2018 May 2

Keywords

  • DNA damage bypass
  • DNA damage checkpoint
  • Exo1
  • postreplication repair
  • replication stress

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint

Dive into the research topics of 'Spatial separation between replisome- and template-induced replication stress signaling'. Together they form a unique fingerprint.

Cite this