Chromosome fragmentation after induction of a double-strand break is an active process prevented by the RMX repair complex.
Chromosome aberrations are common outcomes of exposure to DNA-damaging agents or altered replication events and are associated with various diseases and a variety of carcinomas, including leukemias, lymphomas, sarcomas, and epithelial tumors. The incidence of aberrations can be greatly increased as a result of defects in DNA repair pathways. Although there is considerable information about the molecular events associated with the induction and repair of a double-strand break (DSB), little is known about the events that ultimately lead to translocations or deletions through the formation of chromosome breaks or the dissociation of broken ends. We describe a system for visualizing DNA ends at the site of a DSB in living cells. After induction of the break, DNA ends flanking the DSB site in wild-type cells remained adjacent. Loss of a functional RMX complex (Rad50/Mre11/Xrs2) or a mutation in the Rad50 Zn-hook structure resulted in DNA ends being dispersed in approximately 10%-20% of cells. Thus, the RMX complex holds broken ends together and counteracts mitotic spindle forces that can be destructive to damaged chromosomes.
Lobachev
Kirill
K
Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, 101 Alexander Drive, Research Triangle Park, NC 27709 USA.
Vitriol
Eric
E
Stemple
Jennifer
J
Resnick
Michael A
MA
Bloom
Kerry
K
D015139:Blotting, Southern; D019457:Chromosome Breakage / Q000502:physiology*; D020090:Chromosome Segregation / Q000502:physiology; D053938:DNA Fragmentation / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology*; D045643:DNA Repair Enzymes / Q000378:metabolism* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D008164:Luminescent Proteins; D008938:Mitosis / Q000502:physiology; D009154:Mutation / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D008941:Spindle Apparatus / Q000502:physiology; D015003:Yeasts
D004268:DNA-Binding Proteins; D008164:Luminescent Proteins; C086930:RAD50 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D045643:DNA Repair Enzymes