Chromosome integrity at a double-strand break requires exonuclease 1 and MRX

DNA Repair (Amst). 2011 Jan 2;10(1):102-10. doi: 10.1016/j.dnarep.2010.10.004. Epub 2010 Nov 5.

Abstract

The continuity of duplex DNA is generally considered a prerequisite for chromosome continuity. However, as previously shown in yeast as well as human cells, the introduction of a double-strand break (DSB) does not generate a chromosome break (CRB) in yeast or human cells. The transition from DSB to CRB was found to be under limited control by the tethering function of the RAD50/MRE11/XRS2 (MRX) complex. Using a system for differential fluorescent marking of both sides of an endonuclease-induced DSB in single cells, we found that nearly all DSBs are converted to CRBs in cells lacking both exonuclease 1 (EXO1) activity and MRX complex. Thus, it appears that some feature of exonuclease processing or resection at a DSB is critical for maintaining broken chromosome ends in close proximity. In addition, we discovered a thermal sensitive (cold) component to CRB formation in an MRX mutant that has implications for chromosome end mobility and/or end-processing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Chromosome Breakage
  • Chromosomes, Fungal / metabolism
  • DNA Breaks, Double-Stranded
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • Endodeoxyribonucleases / genetics
  • Endodeoxyribonucleases / metabolism*
  • Exodeoxyribonucleases / genetics
  • Exodeoxyribonucleases / metabolism*
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sequence Deletion
  • Temperature

Substances

  • Saccharomyces cerevisiae Proteins
  • XRS2 protein, S cerevisiae
  • Endodeoxyribonucleases
  • Exodeoxyribonucleases
  • MRE11 protein, S cerevisiae
  • exodeoxyribonuclease I
  • RAD5 protein, S cerevisiae
  • DNA Helicases