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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2009-11-25
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pubmed:abstractText |
During somatic hypermutation (SHM), B cells introduce mutations into their immunoglobulin genes to generate high affinity antibodies. Current models suggest a separation in the generation of G/C transversions by the Ung2-dependent pathway and the generation of A/T mutations by the Msh2/ubiquitinated proliferating cell nuclear antigen (PCNA-Ub)-dependent pathway. It is currently unknown whether these pathways compete to initiate mutagenesis and whether PCNA-Ub functions downstream of Ung2. Furthermore, these models do not explain why mice lacking Msh2 have a more than twofold reduction in the total mutation frequency. Our data indicate that PCNA-Ub is required for A/T mutagenesis downstream of both Msh2 and Ung2. Furthermore, we provide evidence that both pathways are noncompetitive to initiate mutagenesis and even collaborate to generate half of all G/C transversions. These findings significantly add to our understanding of SHM and necessitate an update of present SHM models.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19901081-10662804,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19901081-10835623,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19901081-10912000,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19901081-11007474,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19901081-11106652,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19901081-12401169,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19901081-12555660,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19901081-12819663,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19901081-1420357,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19901081-15939880,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19901081-19414788,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19901081-7628020,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19901081-8751446,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19901081-9115357,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19901081-9697843
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1540-9538
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
23
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pubmed:volume |
206
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2603-11
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pubmed:dateRevised |
2010-9-28
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pubmed:meshHeading |
pubmed-meshheading:19901081-Animals,
pubmed-meshheading:19901081-Antibody Affinity,
pubmed-meshheading:19901081-B-Lymphocytes,
pubmed-meshheading:19901081-Mice,
pubmed-meshheading:19901081-Mice, Mutant Strains,
pubmed-meshheading:19901081-MutS Homolog 2 Protein,
pubmed-meshheading:19901081-Mutation,
pubmed-meshheading:19901081-Proliferating Cell Nuclear Antigen,
pubmed-meshheading:19901081-Somatic Hypermutation, Immunoglobulin,
pubmed-meshheading:19901081-Ubiquitinated Proteins,
pubmed-meshheading:19901081-Uracil-DNA Glycosidase
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pubmed:year |
2009
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pubmed:articleTitle |
Dependence of nucleotide substitutions on Ung2, Msh2, and PCNA-Ub during somatic hypermutation.
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pubmed:affiliation |
Division of Immunology, The Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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