DNA replication meets genetic exchange: chromosomal damage and its repair by homologous recombination.
Proceedings of the National Academy of Sciences Colloquium on the roles of homologous recombination in DNA replication are summarized. Current findings in experimental systems ranging from bacteriophages to mammalian cell lines substantiate the idea that homologous recombination is a system supporting DNA replication when either the template DNA is damaged or the replication machinery malfunctions. There are several lines of supporting evidence: (i) DNA replication aggravates preexisting DNA damage, which then blocks subsequent replication; (ii) replication forks abandoned by malfunctioning replisomes become prone to breakage; (iii) mutants with malfunctioning replisomes or with elevated levels of DNA damage depend on homologous recombination; and (iv) homologous recombination primes DNA replication in vivo and can restore replication fork structures in vitro. The mechanisms of recombinational repair in bacteriophage T4, Escherichia coli, and Saccharomyces cerevisiae are compared. In vitro properties of the eukaryotic recombinases suggest a bigger role for single-strand annealing in the eukaryotic recombinational repair.
Kuzminov
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Department of Microbiology, University of Illinois, Urbana-Champaign, B103, Chemical and Life Sciences Laboratory, 601 South Goodwin Avenue, Urbana, IL 61801-3709, USA. kuzminov@life.uiuc.edu
D000818:Animals; D017122:Bacteriophage T4 / Q000235:genetics; D005075:Biological Evolution; D004249:DNA Damage; D004265:DNA Helicases; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D004260:DNA Repair; D045643:DNA Repair Enzymes; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism; D004706:Endodeoxyribonucleases; D004926:Escherichia coli / Q000235:genetics; D005090:Exodeoxyribonucleases; D005656:Fungal Proteins / Q000378:metabolism; D019426:Integrases; D009692:Nucleic Acid Heteroduplexes; D051721:Rad52 DNA Repair and Recombination Protein; D045522:Recombinases; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D009692:Nucleic Acid Heteroduplexes; C497197:RAD52 protein, S cerevisiae; D051721:Rad52 DNA Repair and Recombination Protein; D045522:Recombinases; D029701:Saccharomyces cerevisiae Proteins; D004254:DNA Nucleotidyltransferases; D019426:Integrases; C115006:integron integrase IntI1; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae; C075468:RAD54 protein, S cerevisiae; D004265:DNA Helicases; D045643:DNA Repair Enzymes