Homologous recombinational repair of DNA ensures mammalian chromosome stability

Larry H. Thompson, David Schild

Research output: Contribution to journalArticle

335 Citations (Scopus)

Abstract

The process of homologous recombinational repair (HRR) is a major DNA repair pathway that acts on double-strand breaks and interstrand crosslinks, and probably to a lesser extent on other kinds of DNA damage. HRR provides a mechanism for the error-free removal of damage present in DNA that has replicated (S and G2 phases). Thus, HRR acts in a critical way, in coordination with the S and G2 checkpoint machinery, to eliminate chromosomal breaks before the cell division occurs. Many of the human HRR genes, including five Rad51 paralogs, have been identified, and knockout mutants for most of these genes are available in chicken DT40 cells. In the mouse, most of the knockout mutations cause embryonic lethality. The Brca1 and Brca2 breast cancer susceptibility genes appear to be intimately involved in HRR, but the mechanistic basis is unknown. Biochemical studies with purified proteins and cell extracts, combined with cytological studies of nuclear foci, have begun to establish an outline of the steps in mammalian HRR. This pathway is subject to complex regulatory controls from the checkpoint machinery and other processes, and there is increasing evidence that loss of HRR gene function can contribute to tumor development. This review article is meant to be an update of our previous review [Biochimie 81 (1999) 87].

Original languageEnglish (US)
Pages (from-to)131-153
Number of pages23
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume477
Issue number1-2
DOIs
StatePublished - Jun 2 2001
Externally publishedYes

Fingerprint

Mammalian Chromosomes
Recombinational DNA Repair
Chromosomal Instability
Genes
Chromosome Breakage
G2 Phase
Neoplasm Genes
Cell Extracts
S Phase
DNA Repair
Cell Division
DNA Damage
Chickens
Breast Neoplasms
Mutation
DNA

Keywords

  • Chromosome
  • DNA
  • Homologous recombinational repair

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Molecular Biology

Cite this

Homologous recombinational repair of DNA ensures mammalian chromosome stability. / Thompson, Larry H.; Schild, David.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 477, No. 1-2, 02.06.2001, p. 131-153.

Research output: Contribution to journalArticle

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