Lack of MSH2 involvement differentiates V(D)J recombination from other non-homologous end joining events

Mani Larijani, Ahmad Zaheen, Darina Frieder, Yuxun Wang, Gillian E. Wu, Winfried Edelmann, Alberto Martin

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

V(D)J recombination and class switch recombination are the two DNA rearrangement events used to diversify the mouse and human antibody repertoires. While their double strand breaks (DSBs) are initiated by different mechanisms, both processes use non-homologous end joining (NHEJ) in the repair phase. DNA mismatch repair elements (MSH2/MSH6) have been implicated in the repair of class switch junctions as well as other DNA DSBs that proceed through NHEJ. MSH2 has also been implicated in the regulation of factors such as ATM and the MRN (Mre11, Rad50, Nbs1) complex, which are involved in V(D)J recombination. These findings led us to examine the role of MSH2 in V(D)J repair. Using MSH2 -/- and MSH2+/+ mice and cell lines, we show here that all pathways involving MSH2 are dispensable for the generation of an intact pre-immune repertoire by V(D)J recombination. In contrast to switch junctions and other DSBs, the usage of terminal homology in V(D)J junctions is not influenced by MSH2. Thus, whether the repair complex for V(D)J recombination is of a canonical NHEJ type or a separate microhomology-mediated-end joining (MMEJ) type, it does not involve MSH2. This highlights a distinction between the repair of V(D)J recombination and other NHEJ reactions.

Original languageEnglish (US)
Pages (from-to)6733-6742
Number of pages10
JournalNucleic Acids Research
Volume33
Issue number21
DOIs
StatePublished - 2005

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V(D)J Recombination
DNA Mismatch Repair
Double-Stranded DNA Breaks
Gene Rearrangement
Genetic Recombination
Cell Line
Antibodies

ASJC Scopus subject areas

  • Genetics

Cite this

Lack of MSH2 involvement differentiates V(D)J recombination from other non-homologous end joining events. / Larijani, Mani; Zaheen, Ahmad; Frieder, Darina; Wang, Yuxun; Wu, Gillian E.; Edelmann, Winfried; Martin, Alberto.

In: Nucleic Acids Research, Vol. 33, No. 21, 2005, p. 6733-6742.

Research output: Contribution to journalArticle

Larijani, Mani ; Zaheen, Ahmad ; Frieder, Darina ; Wang, Yuxun ; Wu, Gillian E. ; Edelmann, Winfried ; Martin, Alberto. / Lack of MSH2 involvement differentiates V(D)J recombination from other non-homologous end joining events. In: Nucleic Acids Research. 2005 ; Vol. 33, No. 21. pp. 6733-6742.
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