title: Mechanics and Single-Molecule Interrogation of DNA Recombination.
abstract: The repair of DNA by homologous recombination is an essential, efficient, and high-fidelity process that mends DNA lesions formed during cellular metabolism; these lesions include double-stranded DNA breaks, daughter-strand gaps, and DNA cross-links. Genetic defects in the homologous recombination pathway undermine genomic integrity and cause the accumulation of gross chromosomal abnormalities-including rearrangements, deletions, and aneuploidy-that contribute to cancer formation. Recombination proceeds through the formation of joint DNA molecules-homologously paired but metastable DNA intermediates that are processed by several alternative subpathways-making recombination a versatile and robust mechanism to repair damaged chromosomes. Modern biophysical methods make it possible to visualize, probe, and manipulate the individual molecules participating in the intermediate steps of recombination, revealing new details about the mechanics of genetic recombination. We review and discuss the individual stages of homologous recombination, focusing on common pathways in bacteria, yeast, and humans, and place particular emphasis on the molecular mechanisms illuminated by single-molecule methods.
authors.affiliation: Department of Microbiology and Molecular Genetics, and Department of Molecular and Cellular Biology, University of California, Davis, California 95616; email: sckowalczykowski@ucdavis.edu.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Bell
authors.affiliation: Department of Microbiology and Molecular Genetics, and Department of Molecular and Cellular Biology, University of California, Davis, California 95616; email: sckowalczykowski@ucdavis.edu.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Kowalczykowski
mesh_terms: D002869:Chromosome Aberrations; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D043211:Exodeoxyribonuclease V / Q000235:genetics / Q000378:metabolism; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D042822:Genomic Instability; D006801:Humans; D051721:Rad52 DNA Repair and Recombination Protein / Q000235:genetics / Q000378:metabolism; D053484:RecQ Helicases / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D059767:Recombinational DNA Repair; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D000072760:Single Molecule Imaging
chemical_list: D004268:DNA-Binding Proteins; C086930:RAD50 protein, S cerevisiae; D051721:Rad52 DNA Repair and Recombination Protein; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae; D043211:Exodeoxyribonuclease V; C506724:RecQ protein, E coli; D053484:RecQ Helicases
keywords: BRCA2; DNA repair; RecA/RAD51; helicase; microscopy; visual biochemistry