pubmed-article:16354685 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:16354685 | lifeskim:mentions | umls-concept:C0374711 | lld:lifeskim |
pubmed-article:16354685 | lifeskim:mentions | umls-concept:C0043240 | lld:lifeskim |
pubmed-article:16354685 | lifeskim:mentions | umls-concept:C1721104 | lld:lifeskim |
pubmed-article:16354685 | lifeskim:mentions | umls-concept:C1704259 | lld:lifeskim |
pubmed-article:16354685 | lifeskim:mentions | umls-concept:C1705987 | lld:lifeskim |
pubmed-article:16354685 | lifeskim:mentions | umls-concept:C1705181 | lld:lifeskim |
pubmed-article:16354685 | lifeskim:mentions | umls-concept:C1523987 | lld:lifeskim |
pubmed-article:16354685 | pubmed:issue | 1 | lld:pubmed |
pubmed-article:16354685 | pubmed:dateCreated | 2005-12-15 | lld:pubmed |
pubmed-article:16354685 | pubmed:abstractText | RAG1 and RAG2 cleave DNA to generate blunt signal ends and hairpin coding ends at antigen receptor loci in lymphoid cells. During V(D)J recombination, repair of these RAG-generated double-strand breaks (DSBs) by the nonhomologous end-joining (NHEJ) pathway contributes substantially to the antigen receptor diversity necessary for immune system function, although recent evidence also supports the ability of RAG-generated breaks to undergo homology-directed repair (HDR). We have determined that RAG-generated chromosomal breaks can be repaired by pathways other than NHEJ in mouse embryonic stem (ES) cells, although repair by these pathways occurs at a significantly lower frequency than NHEJ. HDR frequency was estimated to be >or=40-fold lower than NHEJ frequency for both coding end and signal end reporters. Repair by single-strand annealing was estimated to occur at a comparable or lower frequency than HDR. As expected, V(D)J recombination was substantially impaired in cells deficient for the NHEJ components Ku70, XRCC4, and DNA-PKcs. Concomitant with decreased NHEJ, RAG-induced HDR was increased in each of the mutants, including cells lacking DNA-PKcs, which has been implicated in hairpin opening. HDR was increased to the largest extent in Ku70-/- cells, implicating the Ku70/80 DNA end-binding protein in regulating pathway choice. Thus, RAG-generated DSBs are typically repaired by the NHEJ pathway in ES cells, but in the absence of NHEJ components, a substantial fraction of breaks can be efficiently channeled into alternative pathways in these cells. | lld:pubmed |
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pubmed-article:16354685 | pubmed:language | eng | lld:pubmed |
pubmed-article:16354685 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:16354685 | pubmed:citationSubset | IM | lld:pubmed |
pubmed-article:16354685 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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pubmed-article:16354685 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:16354685 | pubmed:month | Jan | lld:pubmed |
pubmed-article:16354685 | pubmed:issn | 0270-7306 | lld:pubmed |
pubmed-article:16354685 | pubmed:author | pubmed-author:JasinMariaM | lld:pubmed |
pubmed-article:16354685 | pubmed:author | pubmed-author:WeinstockDavi... | lld:pubmed |
pubmed-article:16354685 | pubmed:issnType | Print | lld:pubmed |
pubmed-article:16354685 | pubmed:volume | 26 | lld:pubmed |
pubmed-article:16354685 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:16354685 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:16354685 | pubmed:pagination | 131-9 | lld:pubmed |
pubmed-article:16354685 | pubmed:dateRevised | 2009-11-18 | lld:pubmed |
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pubmed-article:16354685 | pubmed:year | 2006 | lld:pubmed |
pubmed-article:16354685 | pubmed:articleTitle | Alternative pathways for the repair of RAG-induced DNA breaks. | lld:pubmed |