title: Investigations of homologous recombination pathways and their regulation.
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.
authors.affiliation: Molecular Biophysics & Biochemistry, Yale School of Medicine, New Haven, Connecticut.
authors.forename: James M
authors.initials: JM
authors.lastname: Daley
authors.affiliation: Molecular Biophysics & Biochemistry, Yale School of Medicine, New Haven, Connecticut.
authors.forename: YoungHo
authors.initials: Y
authors.lastname: Kwon
authors.affiliation: Molecular Biophysics & Biochemistry, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Hengyao
authors.initials: H
authors.lastname: Niu
authors.affiliation: Molecular Biophysics & Biochemistry, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Patrick
authors.initials: P
authors.lastname: Sung
mesh_terms: D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics*; D045566:DNA, Cruciform / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D059765:Homologous Recombination; D006801:Humans; D008957:Models, Genetic; D051135:Rad51 Recombinase / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D045566:DNA, Cruciform; D004268:DNA-Binding Proteins; D051135:Rad51 Recombinase
keywords: DNA repair; double Holliday junction; double-strand breaks; homologous recombination; presynaptic filament; recombinase; resection; synaptic complex