Chromosome fragmentation after induction of a double-strand break is an active process prevented by the RMX repair complex

Curr Biol. 2004 Dec 14;14(23):2107-12. doi: 10.1016/j.cub.2004.11.051.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Blotting, Southern
  • Chromosome Breakage / physiology*
  • Chromosome Segregation / physiology
  • DNA Fragmentation / physiology*
  • DNA Repair / physiology*
  • DNA Repair Enzymes / metabolism*
  • DNA Repair Enzymes / physiology
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Luminescent Proteins
  • Mitosis / physiology
  • Mutation / genetics
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Spindle Apparatus / physiology
  • Yeasts

Substances

  • DNA-Binding Proteins
  • Luminescent Proteins
  • RAD50 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • DNA Repair Enzymes