Lagging strand maturation factor Dna2 is a component of the replication checkpoint initiation machinery

Sandeep Kumar, Peter M. Burgers

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

Initiation of the DNA replication checkpoint in yeast is mainly mediated by Mec1 protein kinase, the ortholog of human ATR, while its homolog Tel1, the ortholog of human ATM, has a minor replication checkpoint function. Checkpoint initiation requires stimulation of Mec1 kinase activity by specific activators. Saccharomyces cerevisiae Dna2, a nuclease-helicase that is essential for Okazaki fragment maturation, is employed specifically during S phase to stimulate Mec1 kinase and initiate the replication checkpoint. Mutations (W128A and Y130A) in the unstructured N terminus of Dna2 abrogate its checkpoint function in vitro and in vivo. Dna2 shows partial redundancy for the replication checkpoint with checkpoint initiators 9-1-1 (S. cerevisiae Ddc1-Mec3-Rad17 and human Rad9-Rad1-Hus1) and Dpb11, the ortholog of human TopBP1. A triple mutant that eliminates the checkpoint functions of all three initiators abrogates the Mec1-dependent checkpoint.

Original languageEnglish
Pages (from-to)313-321
Number of pages9
JournalGenes and Development
Volume27
Issue number3
DOIs
StatePublished - Feb 1 2013

Keywords

  • 9-1-1
  • ATM
  • ATR
  • Cell cycle checkpoint
  • DNA replication

Fingerprint Dive into the research topics of 'Lagging strand maturation factor Dna2 is a component of the replication checkpoint initiation machinery'. Together they form a unique fingerprint.

Cite this