rdf:type |
|
lifeskim:mentions |
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pubmed:issue |
21
|
pubmed:dateCreated |
2006-12-6
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pubmed:abstractText |
Activation-induced cytidine deaminase (AID) likely initiates immunoglobulin gene-conversion (GC) by deaminating cytidines within the V-region of chicken B-cells. However, the intervening DNA lesion required to initiate GC remains elusive. GC could be initiated by a single strand break or a double strand break (DSB). To distinguish between these possibilities, we examined GC in the chicken DT40 B cell line deficient in non-homologous end joining (NHEJ). It is known that the NHEJ and homologous recombination DNA repair pathways compete for DSBs. In light of this, if a DSB is the major intermediate, deficiency in NHEJ should result in increased levels of GC. Here we show that DNA-PKcs(-/-/-) and Ku70(-/-) DT40 cells had 5- to 10-fold higher levels of GC relative to wildtype DT40 as measured by surface IgM reversion and sequencing of the V-region. These data suggest that a DSB is the major DNA lesion that initiates GC.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
|
pubmed:status |
MEDLINE
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pubmed:issn |
1362-4962
|
pubmed:author |
|
pubmed:issnType |
Electronic
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pubmed:volume |
34
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6345-51
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17142237-Animals,
pubmed-meshheading:17142237-Antigens, Nuclear,
pubmed-meshheading:17142237-Cell Line,
pubmed-meshheading:17142237-Chickens,
pubmed-meshheading:17142237-DNA Breaks, Double-Stranded,
pubmed-meshheading:17142237-DNA Repair,
pubmed-meshheading:17142237-DNA-Activated Protein Kinase,
pubmed-meshheading:17142237-DNA-Binding Proteins,
pubmed-meshheading:17142237-Gene Conversion,
pubmed-meshheading:17142237-Gene Deletion,
pubmed-meshheading:17142237-Genes, Immunoglobulin,
pubmed-meshheading:17142237-Immunoglobulin M
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pubmed:year |
2006
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pubmed:articleTitle |
NHEJ-deficient DT40 cells have increased levels of immunoglobulin gene conversion: evidence for a double strand break intermediate.
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pubmed:affiliation |
Department of Immunology, 5265 Medical Sciences Building, University of Toronto, Ontario, Toronto, Canada M5S 1A8.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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