Delineation of the role of the Mre11 complex in class switch recombination

A Lahdesmaki, Alexander Taylor, KH Chrzanowska, Q Pan-Hammarstrom

Research output: Contribution to journalArticle

65 Citations (Scopus)


Class switch recombination (CSR) is a region-specific, transcriptionally regulated, nonhomologous recombinational process that is initiated by activation-induced cytidine deaminase (AID). The initial lesions in the switch (S) regions are processed and resolved, leading to a recombination of the two S regions involved. The mechanism involved in the repair and ligation of the broken DNA ends is however still unclear. Here, we describe that switching is less efficient in cells from patients with Mre11 deficiency (Ataxia-Telangiectasia-like disorder, ATLD) and, more importantly, that the switch recombination junctions resulting from the in vivo switching events are aberrant. There was a trend toward an increased usage of microhomology (> or =4 bp) at the switch junctions in both ATLD and Nijmegen breakage syndrome (NBS) patients. However, the DNA ends were not joined as "perfectly" as those from Ataxia-Telangiectasia (A-T) patients and 1-2 bp mutations or insertions were often observed. In switch junctions from ATLD patients, there were fewer base substitutions due to transitions and, most strikingly, the substitutions that occurred most often in controls, C --> T transitions, never occurred at, or close to, the junctions derived from the ATLD patients. In switch junctions from NBS patients, all base substitutions were observed at the G/C nucleotides, and transitions were preferred. These data suggest that the Mre11-Rad50-Nbs1 complex (Mre11 complex) is involved in the nonhomologous end joining pathway in CSR and that Mre11, Nbs1, and protein mutated in ataxia-telangiectasia (ATM) might have both common and independent roles in this process.
Original languageEnglish
Pages (from-to)16479-16487
Number of pages9
JournalJournal of Biological Chemistry
Publication statusPublished - 1 Jan 2004


Dive into the research topics of 'Delineation of the role of the Mre11 complex in class switch recombination'. Together they form a unique fingerprint.

Cite this