Investigations of homologous recombination pathways and their regulation

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

The DNA double-strand break (DSB), arising from exposure to ionizing radiation or various chemotherapeutic agents or from replication fork collapse, is among the most dangerous of chromosomal lesions. DSBs are highly cytotoxic and can lead to translocations, deletions, duplications, or mutations if mishandled. DSBs are eliminated by either homologous recombination (HR), which uses a homologous template to guide accurate repair, or by nonhomologous end joining (NHEJ), which simply rejoins the two broken ends after damaged nucleotides have been removed. HR generates error-free repair products and is also required for generating chromosome arm crossovers between homologous chromosomes in meiotic cells. The HR reaction includes several distinct steps: resection of DNA ends, homologous DNA pairing, DNA synthesis, and processing of HR intermediates. Each occurs in a highly regulated fashion utilizing multiple protein factors. These steps are being elucidated using a combination of genetic tools, cell-based assays, and in vitro reconstitution with highly purified HR proteins. In this review, we summarize contributions from our laboratory at Yale University in understanding HR mechanisms in eukaryotic cells.

Original languageEnglish (US)
Pages (from-to)453-461
Number of pages9
JournalYale Journal of Biology and Medicine
Volume86
Issue number4
StatePublished - Dec 2013
Externally publishedYes

Keywords

  • DNA repair
  • Double Holliday junction
  • Double-strand breaks
  • Homologous recombination
  • Presynaptic filament
  • Recombinase
  • Resection
  • Synaptic complex

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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