Chromosomal stability and the DNA double-stranded break connection.
Genome stability is of primary importance for the survival and proper functioning of all organisms. Double-stranded breaks in DNA are important threats to genome integrity because they can result in chromosomal aberrations that can affect, simultaneously, many genes, and lead to cell malfunctioning and cell death. These detrimental consequences are counteracted by two mechanistically distinct pathways of double-stranded break repair: homologous recombination and non-homologous end-joining. Recently, unexpected links between these double-stranded break-repair systems, and several human genome instability and cancer predisposition syndromes, have emerged. Now, interactions between both double-stranded break-repair pathways and other cellular processes, such as cell-cycle regulation and replication, are being unveiled.
Department of Cell Biology and Genetics, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands. vangent@gen.fgg.eur.nl
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van Gent
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Hoeijmakers
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Kanaar
D000818:Animals; D001260:Ataxia Telangiectasia / Q000235:genetics; D030161:Avian Proteins; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002645:Chickens; D002869:Chromosome Aberrations; D004247:DNA / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics; D051379:Mice; D008957:Models, Genetic; D009154:Mutation; D011494:Protein Kinases / Q000235:genetics*; D051135:Rad51 Recombinase; D011839:Radiation, Ionizing; D011995:Recombination, Genetic; D013577:Syndrome
D030161:Avian Proteins; D004268:DNA-Binding Proteins; D007074:Immunoglobulin G; D004247:DNA; D011494:Protein Kinases; C495150:RAD51 protein, Gallus gallus; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; C495154:Rad51 protein, mouse