Toward maintaining the genome: DNA damage and replication checkpoints

Kara A. Nyberg, Rhett J. Michelson, Charles W. Putnam, Ted A. Weinert

Research output: Contribution to journalReview articlepeer-review

652 Scopus citations


DNA checkpoints play a significant role in cancer pathology, perhaps most notably in maintaining genome stability. This review summarizes the genetic and molecular mechanisms of checkpoint activation in response to DNA damage. The major checkpoint proteins common to all eukaryotes are identified and discussed, together with how the checkpoint proteins interact to induce arrest within each cell cycle phase. Also discussed are the molecular signals that activate checkpoint responses, including single-strand DNA, double-strand breaks, and aberrant replication forks. We address the connection between checkpoint proteins and damage repair mechanisms, how cells recover from an arrest response, and additional roles that checkpoint proteins play in DNA metabolism. Finally, the connection between checkpoint gene mutation and genomic instability is considered.

Original languageEnglish (US)
Pages (from-to)617-656
Number of pages40
JournalAnnual review of genetics
StatePublished - 2002


  • ATM
  • BRCA1
  • Genomic instability
  • Repair
  • p53

ASJC Scopus subject areas

  • Genetics


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