| pubmed-article:21653319 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:21653319 | lifeskim:mentions | umls-concept:C0023418 | lld:lifeskim |
| pubmed-article:21653319 | lifeskim:mentions | umls-concept:C1158512 | lld:lifeskim |
| pubmed-article:21653319 | lifeskim:mentions | umls-concept:C1419240 | lld:lifeskim |
| pubmed-article:21653319 | lifeskim:mentions | umls-concept:C0599894 | lld:lifeskim |
| pubmed-article:21653319 | pubmed:issue | 4 | lld:pubmed |
| pubmed-article:21653319 | pubmed:dateCreated | 2011-7-29 | lld:pubmed |
| pubmed-article:21653319 | pubmed:abstractText | Chronic myeloid leukemia chronic phase (CML-CP) CD34(+) cells contain numerous DNA double-strand breaks whose unfaithful repair may contribute to chromosomal instability and disease progression to blast phase (CML-BP). These phenomena are often associated with the appearance of imatinib-resistant BCR-ABL1 kinase mutants (eg, T315I) and overexpression of BCR-ABL1. Here we show that BCR-ABL1 (nonmutated and T315I mutant) promoted RAD51 recombinase-mediated unfaithful homeologous recombination repair (HomeoRR) in a dosage-dependent manner. BCR-ABL1 SH3 domain interacts with RAD51 proline-rich regions, resulting in direct phosphorylation of RAD51 on Y315 (pY315). RAD51(pY315) facilitates dissociation from the complex with BCR-ABL1 kinase, migrates to the nucleus, and enhances formation of the nuclear foci indicative of recombination sites. HomeoRR and RAD51 nuclear foci were strongly reduced by RAD51(Y315F) phosphorylation-less mutant. In addition, peptide aptamer mimicking RAD51(pY315) fragment, but not that with Y315F phosphorylation-less substitution, diminished RAD51 foci formation and inhibited HomeoRR in leukemia cells. In conclusion, we postulate that BCR-ABL1 kinase-mediated RAD51(pY315) promotes unfaithful HomeoRR in leukemia cells, which may contribute to accumulation of secondary chromosomal aberrations responsible for CML relapse and progression. | lld:pubmed |
| pubmed-article:21653319 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21653319 | pubmed:language | eng | lld:pubmed |
| pubmed-article:21653319 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21653319 | pubmed:citationSubset | AIM | lld:pubmed |
| pubmed-article:21653319 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21653319 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21653319 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21653319 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:21653319 | pubmed:month | Jul | lld:pubmed |
| pubmed-article:21653319 | pubmed:issn | 1528-0020 | lld:pubmed |
| pubmed-article:21653319 | pubmed:author | pubmed-author:SkorskiTomasz... | lld:pubmed |
| pubmed-article:21653319 | pubmed:author | pubmed-author:RenShu-YueSY | lld:pubmed |
| pubmed-article:21653319 | pubmed:author | pubmed-author:SlupianekArtu... | lld:pubmed |
| pubmed-article:21653319 | pubmed:author | pubmed-author:FleuryFabrice... | lld:pubmed |
| pubmed-article:21653319 | pubmed:author | pubmed-author:Nieborowska-S... | lld:pubmed |
| pubmed-article:21653319 | pubmed:author | pubmed-author:GurdekEwaE | lld:pubmed |
| pubmed-article:21653319 | pubmed:author | pubmed-author:DasguptaYasho... | lld:pubmed |
| pubmed-article:21653319 | pubmed:author | pubmed-author:DonlinMileneM | lld:pubmed |
| pubmed-article:21653319 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:21653319 | pubmed:day | 28 | lld:pubmed |
| pubmed-article:21653319 | pubmed:volume | 118 | lld:pubmed |
| pubmed-article:21653319 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:21653319 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:21653319 | pubmed:pagination | 1062-8 | lld:pubmed |
| pubmed-article:21653319 | pubmed:meshHeading | pubmed-meshheading:21653319... | lld:pubmed |
| pubmed-article:21653319 | pubmed:meshHeading | pubmed-meshheading:21653319... | lld:pubmed |
| pubmed-article:21653319 | pubmed:meshHeading | pubmed-meshheading:21653319... | lld:pubmed |
| pubmed-article:21653319 | pubmed:meshHeading | pubmed-meshheading:21653319... | lld:pubmed |
| pubmed-article:21653319 | pubmed:meshHeading | pubmed-meshheading:21653319... | lld:pubmed |
| pubmed-article:21653319 | pubmed:meshHeading | pubmed-meshheading:21653319... | lld:pubmed |
| pubmed-article:21653319 | pubmed:meshHeading | pubmed-meshheading:21653319... | lld:pubmed |
| pubmed-article:21653319 | pubmed:meshHeading | pubmed-meshheading:21653319... | lld:pubmed |
| pubmed-article:21653319 | pubmed:meshHeading | pubmed-meshheading:21653319... | lld:pubmed |
| pubmed-article:21653319 | pubmed:meshHeading | pubmed-meshheading:21653319... | lld:pubmed |
| pubmed-article:21653319 | pubmed:meshHeading | pubmed-meshheading:21653319... | lld:pubmed |
| pubmed-article:21653319 | pubmed:meshHeading | pubmed-meshheading:21653319... | lld:pubmed |
| pubmed-article:21653319 | pubmed:year | 2011 | lld:pubmed |
| pubmed-article:21653319 | pubmed:articleTitle | Targeting RAD51 phosphotyrosine-315 to prevent unfaithful recombination repair in BCR-ABL1 leukemia. | lld:pubmed |
| pubmed-article:21653319 | pubmed:affiliation | Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, PA, USA. | lld:pubmed |
| pubmed-article:21653319 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:21653319 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| pubmed-article:21653319 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
| entrez-gene:5888 | entrezgene:pubmed | pubmed-article:21653319 | lld:entrezgene |
| entrez-gene:19361 | entrezgene:pubmed | pubmed-article:21653319 | lld:entrezgene |
| http://linkedlifedata.com/r... | entrezgene:pubmed | pubmed-article:21653319 | lld:entrezgene |
| http://linkedlifedata.com/r... | entrezgene:pubmed | pubmed-article:21653319 | lld:entrezgene |
