Functional antibody genes are assembled by V-D-J joining and then diversified by somatic hypermutation. This hypermutation results from stepwise incorporation of single nucleotide substitutions into the V gene, underpinning much of antibody diversity and affinity maturation. Hypermutation is triggered by activation-induced deaminase (AID), an enzyme which catalyzes targeted deamination of deoxycytidine residues in DNA. The pathways used for processing the AID-generated U:G lesions determine the variety of base substitutions observed during somatic hypermutation. Thus, DNA replication across the uracil yields transition mutations at C:G pairs, whereas uracil excision by UNG uracil-DNA glycosylase creates abasic sites that can also yield transversions. Recognition of the U:G mismatch by MSH2/MSH6 triggers a mutagenic patch repair in which polymerase eta plays a major role and leads to mutations at A:T pairs. AID-triggered DNA deamination also underpins immunoglobulin variable (IgV) gene conversion, isotype class switching, and some oncogenic translocations in B cell tumors.
%0 Journal Article
%1 dinoia2007molecular
%A Di Noia, J M
%A Neuberger, M S
%D 2007
%J Annu Rev Biochem
%K B_cells context-dependent-mutation review somatic_hypermutation somatic_mutation
%P 1-22
%R 10.1146/annurev.biochem.76.061705.090740
%T Molecular mechanisms of antibody somatic hypermutation
%U https://www.ncbi.nlm.nih.gov/pubmed/17328676
%V 76
%X Functional antibody genes are assembled by V-D-J joining and then diversified by somatic hypermutation. This hypermutation results from stepwise incorporation of single nucleotide substitutions into the V gene, underpinning much of antibody diversity and affinity maturation. Hypermutation is triggered by activation-induced deaminase (AID), an enzyme which catalyzes targeted deamination of deoxycytidine residues in DNA. The pathways used for processing the AID-generated U:G lesions determine the variety of base substitutions observed during somatic hypermutation. Thus, DNA replication across the uracil yields transition mutations at C:G pairs, whereas uracil excision by UNG uracil-DNA glycosylase creates abasic sites that can also yield transversions. Recognition of the U:G mismatch by MSH2/MSH6 triggers a mutagenic patch repair in which polymerase eta plays a major role and leads to mutations at A:T pairs. AID-triggered DNA deamination also underpins immunoglobulin variable (IgV) gene conversion, isotype class switching, and some oncogenic translocations in B cell tumors.
@article{dinoia2007molecular,
abstract = {Functional antibody genes are assembled by V-D-J joining and then diversified by somatic hypermutation. This hypermutation results from stepwise incorporation of single nucleotide substitutions into the V gene, underpinning much of antibody diversity and affinity maturation. Hypermutation is triggered by activation-induced deaminase (AID), an enzyme which catalyzes targeted deamination of deoxycytidine residues in DNA. The pathways used for processing the AID-generated U:G lesions determine the variety of base substitutions observed during somatic hypermutation. Thus, DNA replication across the uracil yields transition mutations at C:G pairs, whereas uracil excision by UNG uracil-DNA glycosylase creates abasic sites that can also yield transversions. Recognition of the U:G mismatch by MSH2/MSH6 triggers a mutagenic patch repair in which polymerase eta plays a major role and leads to mutations at A:T pairs. AID-triggered DNA deamination also underpins immunoglobulin variable (IgV) gene conversion, isotype class switching, and some oncogenic translocations in B cell tumors.},
added-at = {2017-05-31T07:18:50.000+0200},
author = {Di Noia, J M and Neuberger, M S},
biburl = {https://www.bibsonomy.org/bibtex/22c80b0d5f1a7c1c8782810223d26cf56/peter.ralph},
doi = {10.1146/annurev.biochem.76.061705.090740},
interhash = {35f2b17b0042481479800a7da33d5615},
intrahash = {2c80b0d5f1a7c1c8782810223d26cf56},
journal = {Annu Rev Biochem},
keywords = {B_cells context-dependent-mutation review somatic_hypermutation somatic_mutation},
pages = {1-22},
pmid = {17328676},
timestamp = {2017-05-31T07:18:50.000+0200},
title = {Molecular mechanisms of antibody somatic hypermutation},
url = {https://www.ncbi.nlm.nih.gov/pubmed/17328676},
volume = 76,
year = 2007
}