Linking double-stranded DNA breaks to the recombination activating gene complex directs repair to the nonhomologous end-joining pathway

Xiaoping Cui and
Katheryn Meek*

College of Veterinary Medicine and Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824

Edited by Martin Gellert, National Institutes of Health, Bethesda, MD, and approved August 29, 2007 (received for review December 8, 2006)

Abstract

Two major DNA repair pathways, nonhomologous end-joining (NHEJ) and homologous recombination (HR), repair double-stranded DNA breaks (DSBs) in all eukaryotes. Additionally, several alternative end-joining pathways (or subpathways) have been reported that characteristically use short-sequence homologies at the DNA ends to facilitate joining. How a cell chooses which DNA repair pathway to use (at any particular DSB) is a central and largely unanswered question. For one type of DSB, there is apparently no choice. DSBs mediated by the lymphocyte-specific recombination activating gene (RAG) endonuclease are repaired virtually exclusively by NHEJ. Here we demonstrate that non-RAG-mediated DSBs can be similarly forced into the NHEJ pathway by physical association with the RAG endonuclease.

Footnotes

*To whom all correspondence should be addressed. E-mail: kmeek{at}msu.edu
Author contributions: X.C. and K.M. designed research; X.C. and K.M. performed research; and K.M. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0610928104/DC1.
Abbreviations:

NHEJ,

nonhomologous end-joining;

HR,

homologous recombination;

DSB,

double-stranded DNA break;

RAG,

recombination-activating gene;

RSS,

recombination signal sequence;

LMPCR,

ligation-mediated PCR.