The MRE11-RAD50-NBS1 complex accelerates somatic hypermutation and gene conversion of immunoglobulin variable regions
- 5 June 2005
- journal article
- research article
- Published by Springer Nature in Nature Immunology
- Vol. 6 (7) , 730-736
- https://doi.org/10.1038/ni1215
Abstract
Targeted diversification of immunoglobulin variable regions is induced by activation-induced deaminase and may occur by either somatic hypermutation or gene conversion. MRE11-RAD50-NBS1 (MRN) is a ubiquitous and conserved nuclease complex critical for DNA break repair and is essential in class-switch recombination. Here we show that ectopic expression of NBS1, the regulatory subunit of MRN, accelerated hypermutation in the human B cell line Ramos and accelerated gene conversion in the chicken B cell line DT40. In both cases, accelerated diversification depended on MRN complex formation. These data suggest that MRN promotes DNA cleavage and/or mutagenic repair of lesions initiated by activation-induced deaminase, acting in the shared pathway of immunoglobulin gene diversification.Keywords
This publication has 50 references indexed in Scilit:
- Repair and Genetic Consequences of Endogenous DNA Base Damage in Mammalian CellsAnnual Review of Genetics, 2004
- Transcription enhances AID-mediated cytidine deamination by exposing single-stranded DNA on the nontemplate strandNature Immunology, 2003
- Transcription-targeted DNA deamination by the AID antibody diversification enzymeNature, 2003
- Activation-induced cytidine deaminase deaminates deoxycytidine on single-stranded DNA but requires the action of RNaseProceedings of the National Academy of Sciences, 2003
- Altering the pathway of immunoglobulin hypermutation by inhibiting uracil-DNA glycosylaseNature, 2002
- AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversificationNature, 2002
- AID Is Essential for Immunoglobulin V Gene Conversion in a Cultured B Cell LineCurrent Biology, 2002
- Requirement of the Activation-Induced Deaminase ( AID ) Gene for Immunoglobulin Gene ConversionScience, 2002
- Class Switch Recombination and Hypermutation Require Activation-Induced Cytidine Deaminase (AID), a Potential RNA Editing EnzymeCell, 2000
- Activation-Induced Cytidine Deaminase (AID) Deficiency Causes the Autosomal Recessive Form of the Hyper-IgM Syndrome (HIGM2)Cell, 2000