Source:http://linkedlifedata.com/resource/pubmed/id/17015724
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
2006-10-3
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pubmed:abstractText |
Somatic hypermutation (SHM) and class switch recombination (CSR) are initiated by activation-induced cytosine deaminase (AID). The uracil, and potentially neighboring bases, are processed by error-prone base excision repair and mismatch repair. Deficiencies in Ung, Msh2, or Msh6 affect SHM and CSR. To determine whether Msh2/Msh6 complexes which recognize single-base mismatches and loops were the only mismatch-recognition complexes required for SHM and CSR, we analyzed these processes in Msh6(-/-)Ung(-/-) mice. SHM and CSR were affected in the same degree and fashion as in Msh2(-/-)Ung(-/-) mice; mutations were mostly C,G transitions and CSR was greatly reduced, making Msh2/Msh3 contributions unlikely. Inactivating Ung alone reduced mutations from A and T, suggesting that, depending on the DNA sequence, varying proportions of A,T mutations arise by error-prone long-patch base excision repair. Further, in Msh6(-/-)Ung(-/-) mice the 5' end and the 3' region of Ig genes was spared from mutations as in wild-type mice, confirming that AID does not act in these regions. Finally, because in the absence of both Ung and Msh6, transition mutations from C and G likely are "footprints" of AID, the data show that the activity of AID is restricted drastically in vivo compared with AID in cell-free assays.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/AICDA (activation-induced cytidine...,
http://linkedlifedata.com/resource/pubmed/chemical/Cytidine Deaminase,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Glycosylases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Msh6 protein, mouse
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
177
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5386-92
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pubmed:dateRevised |
2007-12-3
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pubmed:meshHeading |
pubmed-meshheading:17015724-Animals,
pubmed-meshheading:17015724-Base Pair Mismatch,
pubmed-meshheading:17015724-Cytidine Deaminase,
pubmed-meshheading:17015724-DNA Glycosylases,
pubmed-meshheading:17015724-DNA Mismatch Repair,
pubmed-meshheading:17015724-DNA-Binding Proteins,
pubmed-meshheading:17015724-Immunoglobulin Class Switching,
pubmed-meshheading:17015724-Mice,
pubmed-meshheading:17015724-Mice, Knockout,
pubmed-meshheading:17015724-Somatic Hypermutation, Immunoglobulin
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pubmed:year |
2006
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pubmed:articleTitle |
Somatic hypermutation and class switch recombination in Msh6(-/-)Ung(-/-) double-knockout mice.
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pubmed:affiliation |
Department of Molecular Genetic and Cell Biology, University of Chicago, Chicago, IL 60637, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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