Advertisement

Quality control of DNA break metabolism: in the ‘end’, it's a good thing

Roland Kanaar, Claire Wyman, Rodney Rothstein

Author Affiliations

  1. Roland Kanaar*,1,2,
  2. Claire Wyman1,2 and
  3. Rodney Rothstein3
  1. 1 Department of Cell Biology and Genetics, Cancer Genomics Center, Erasmus Medical Center, Rotterdam, The Netherlands
  2. 2 Department of Radiation Oncology, Erasmus Medical Center, Rotterdam, The Netherlands
  3. 3 Department of Genetics and Development, Columbia University Medical Center, New York, NY, USA
  1. *Corresponding author. Department of Cell Biology and Genetics, Cancer Genomics Center, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands. Tel.: +31 10 704 3168; Fax: +31 10 704 4747; E-mail: r.kanaar{at}erasmusmc.nl
View Full Text

Abstract

DNA ends pose specific problems in the control of genetic information quality. Ends of broken DNA need to be rejoined to avoid genome rearrangements, whereas natural DNA ends of linear chromosomes, telomeres, need to be stable and hidden from the DNA damage response. Efficient DNA end metabolism, either at induced DNA breaks or telomeres, does not result from the machine‐like precision of molecular reactions, but rather from messier, more stochastic processes. The necessary molecular interactions are dynamically unstable, with constructive and destructive processes occurring in competition. In the end, quality control comes from the constant building up and tearing down of inappropriate, but also appropriate reaction steps in combination with factors that only slightly shift the equilibrium to eventually favour appropriate events. Thus, paradoxically, enzymes antagonizing DNA end metabolism help to ensure that genome maintenance becomes a robust process.

  • Received December 13, 2007.
  • Accepted January 14, 2008.
View Full Text