Disruption of mechanisms that prevent rereplication triggers a DNA damage response

Vincent Archambault, Amy E. Ikui, Benjamin J. Drapkin, Frederick R. Cross

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Eukaryotes replicate DNA once and only once per cell cycle due to multiple, partially overlapping mechanisms efficiently preventing reinitiation. The consequences of reinitiation are unknown. Here we show that the induction of rereplication by mutations in components of the prereplicative complex (origin recognition complex [ORC], Cdc6, and minichromosome maintenance proteins) causes a cell cycle arrest with activated Rad53, a large-budded morphology, and an undivided nucleus. Combining a mutation disrupting the CIb5-Orc6 interaction (ORC6-rxl) and a mutation stabilizing Cdc6 (CDC6ΔNT) causes a cell cycle delay with a similar phenotype, although this background is only partially compromised for rereplication control and does not exhibit overreplication detectable by fluorescence-activated cell sorting. We conducted a systematic screen that identified genetic requirements for the viability of these cells. ORC6-rxl CDC6ΔNT cells depend heavily on genes required for the DNA damage response and for double-strand-break repair by homologous recombination. Our results implicate an Mre11-Mec1-dependent pathway in limiting the extent of rereplication.

Original languageEnglish (US)
Pages (from-to)6707-6721
Number of pages15
JournalMolecular and cellular biology
Issue number15
StatePublished - Aug 2005
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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