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

Kirill Lobachev, Eric Vitriol, Jennifer Stemple, Michael A. Resnick, Kerry Bloom

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

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 [1, 2]. The incidence of aberrations can be greatly increased as a result of defects in DNA repair pathways [3]. 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.

Original languageEnglish (US)
Pages (from-to)2107-2112
Number of pages6
JournalCurrent Biology
Volume14
Issue number23
DOIs
StatePublished - Dec 14 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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