Altered somatic hypermutation and reduced class-switch recombination in exonuclease 1-mutant mice.
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.
Bardwell
Philip D
PD
Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Woo
Caroline J
CJ
Wei
Kaichun
K
Li
Ziqiang
Z
Martin
Alberto
A
Sack
Stephen Z
SZ
Parris
Tchaiko
T
Edelmann
Winfried
W
Scharff
Matthew D
MD
D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D020137:Base Pair Mismatch; D002460:Cell Line; D004260:DNA Repair; D045643:DNA Repair Enzymes; D005090:Exodeoxyribonucleases / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D017578:Immunoglobulin Class Switching; D051379:Mice; D011995:Recombination, Genetic; D027041:Somatic Hypermutation, Immunoglobulin
C114331:EXO1 protein, human; D005090:Exodeoxyribonucleases; C028450:exodeoxyribonuclease I; D045643:DNA Repair Enzymes