MRN complex function in the repair of chromosomal Rag-mediated DNA double-strand breaks Academic Article uri icon

Overview

MeSH Major

  • ATP-Binding Cassette Transporters
  • Cell Cycle Proteins
  • Chromosomes, Mammalian
  • DNA Breaks, Double-Stranded
  • DNA Repair
  • DNA Repair Enzymes
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Nuclear Proteins

abstract

  • The Mre11-Rad50-Nbs1 (MRN) complex functions in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) at postreplicative stages of the cell cycle. During HR, the MRN complex functions directly in the repair of DNA DSBs and in the initiation of DSB responses through activation of the ataxia telangiectasia-mutated (ATM) serine-threonine kinase. Whether MRN functions in DNA damage responses before DNA replication in G0/G1 phase cells has been less clear. In developing G1-phase lymphocytes, DNA DSBs are generated by the Rag endonuclease and repaired during the assembly of antigen receptor genes by the process of V(D)J recombination. Mice and humans deficient in MRN function exhibit lymphoid phenotypes that are suggestive of defects in V(D)J recombination. We show that during V(D)J recombination, MRN deficiency leads to the aberrant joining of Rag DSBs and to the accumulation of unrepaired coding ends, thus establishing a functional role for MRN in the repair of Rag-mediated DNA DSBs. Moreover, these defects in V(D)J recombination are remarkably similar to those observed in ATM-deficient lymphocytes, suggesting that ATM and MRN function in the same DNA DSB response pathways during lymphocyte antigen receptor gene assembly.

publication date

  • March 16, 2009

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2699138

Digital Object Identifier (DOI)

  • 10.1084/jem.20081326

PubMed ID

  • 19221393

Additional Document Info

start page

  • 669

end page

  • 79

volume

  • 206

number

  • 3