TY - JOUR
T1 - Somatic hypermutation in MutS homologue (MSH)3-, MSH6-, and MSH3/MSH6-deficient mice reveals a role for the MSH2-MSH6 heterodimer in modulating the base substitution pattern
AU - Wiesendanger, Margrit
AU - Kneitz, Burkhard
AU - Edelmann, Winfried
AU - Scharff, Matthew D.
PY - 2000/2/7
Y1 - 2000/2/7
N2 - Although the primary function of the DNA mismatch repair (MMR) system is to identify and correct base mismatches that have been erroneously introduced during DNA replication, recent studies have further implicated several MMR components in somatic hypermutation of immunoglobulin (Ig) genes. We studied the immune response in mice deficient in MutS homologue (MSH)3 and MSH6, two mutually exclusive partners of MSH2 that have not been examined previously for their role in Ig hypermutation. In Msh6(-/-) and Msh3(-/-)/Msh6(-/-) mice, base substitutions are preferentially targeted to G and C nucleotides and to an RGYW hot spot, as has been shown previously in Msh2(-/-) mice. In contrast, Msh3(-/-) mice show no differences from their littermate controls. These findings indicate that the MSH2-MSH6 heterodimer, but not the MSH2-MSH3 complex, is responsible for modulating Ig hypermutation.
AB - Although the primary function of the DNA mismatch repair (MMR) system is to identify and correct base mismatches that have been erroneously introduced during DNA replication, recent studies have further implicated several MMR components in somatic hypermutation of immunoglobulin (Ig) genes. We studied the immune response in mice deficient in MutS homologue (MSH)3 and MSH6, two mutually exclusive partners of MSH2 that have not been examined previously for their role in Ig hypermutation. In Msh6(-/-) and Msh3(-/-)/Msh6(-/-) mice, base substitutions are preferentially targeted to G and C nucleotides and to an RGYW hot spot, as has been shown previously in Msh2(-/-) mice. In contrast, Msh3(-/-) mice show no differences from their littermate controls. These findings indicate that the MSH2-MSH6 heterodimer, but not the MSH2-MSH3 complex, is responsible for modulating Ig hypermutation.
KW - DNA mismatch repair
KW - Germinal center
KW - Immunoglobulin genes
KW - Msh3
KW - Msh6
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U2 - 10.1084/jem.191.3.579
DO - 10.1084/jem.191.3.579
M3 - Article
C2 - 10662804
AN - SCOPUS:0034614916
SN - 0022-1007
VL - 191
SP - 579
EP - 584
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 3
ER -