Altered somatic hypermutation and reduced class-switch recombination in exonuclease 1-mutant mice

Philip D. Bardwell; Caroline J. Woo; Kaichun Wei; Ziqiang Li; Alberto Martin; Stephen Z. Sack; Tchaiko Parris; Winfried Edelmann; Matthew D. Scharff

doi:10.1038/ni1031

Altered somatic hypermutation and reduced class-switch recombination in exonuclease 1-mutant mice

Philip D. Bardwell, Caroline J. Woo, Kaichun Wei, Ziqiang Li, Alberto Martin, Stephen Z. Sack, Tchaiko Parris, Winfried Edelmann, Matthew D. Scharff

Cell Biology

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220 Scopus citations

Abstract

The generation of protective antibodies requires somatic hypermutation (SHM) and class-switch recombination (CSR) of immunoglobulin genes. Here we show that mice mutant for exonuclease 1 (Exo1), which participates in DNA mismatch repair (MMR), have decreased CSR and changes in the characteristics of SHM similar to those previously observed in mice mutant for the MMR protein Msh2. Exo1 is thus the first exonuclease shown to be involved in SHM and CSR. The phenotype of Exo1^-/- mice and the finding that Exo1 and Mlh1 are physically associated with mutating variable regions support the idea that Exo1 and MMR participate directly in SHM and CSR.

Original language	English (US)
Pages (from-to)	224-229
Number of pages	6
Journal	Nature Immunology
Volume	5
Issue number	2
DOIs	https://doi.org/10.1038/ni1031
State	Published - Feb 2004

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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title = "Altered somatic hypermutation and reduced class-switch recombination in exonuclease 1-mutant mice",

abstract = "The generation of protective antibodies requires somatic hypermutation (SHM) and class-switch recombination (CSR) of immunoglobulin genes. Here we show that mice mutant for exonuclease 1 (Exo1), which participates in DNA mismatch repair (MMR), have decreased CSR and changes in the characteristics of SHM similar to those previously observed in mice mutant for the MMR protein Msh2. Exo1 is thus the first exonuclease shown to be involved in SHM and CSR. The phenotype of Exo1-/- mice and the finding that Exo1 and Mlh1 are physically associated with mutating variable regions support the idea that Exo1 and MMR participate directly in SHM and CSR.",

author = "Bardwell, {Philip D.} and Woo, {Caroline J.} and Kaichun Wei and Ziqiang Li and Alberto Martin and Sack, {Stephen Z.} and Tchaiko Parris and Winfried Edelmann and Scharff, {Matthew D.}",

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T1 - Altered somatic hypermutation and reduced class-switch recombination in exonuclease 1-mutant mice

AU - Bardwell, Philip D.

AU - Woo, Caroline J.

AU - Wei, Kaichun

AU - Li, Ziqiang

AU - Martin, Alberto

AU - Sack, Stephen Z.

AU - Parris, Tchaiko

AU - Edelmann, Winfried

AU - Scharff, Matthew D.

PY - 2004/2

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AB - The generation of protective antibodies requires somatic hypermutation (SHM) and class-switch recombination (CSR) of immunoglobulin genes. Here we show that mice mutant for exonuclease 1 (Exo1), which participates in DNA mismatch repair (MMR), have decreased CSR and changes in the characteristics of SHM similar to those previously observed in mice mutant for the MMR protein Msh2. Exo1 is thus the first exonuclease shown to be involved in SHM and CSR. The phenotype of Exo1-/- mice and the finding that Exo1 and Mlh1 are physically associated with mutating variable regions support the idea that Exo1 and MMR participate directly in SHM and CSR.

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Altered somatic hypermutation and reduced class-switch recombination in exonuclease 1-mutant mice

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