| An mre11 mutation that promotes telomere recombination and an efficient bypass of senescence. | |
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MedLine Citation:
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PMID: 20421597 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Preventing the formation of dysfunctional telomeres is essential for genomic stability. In most organisms, the ribo-nucleoprotein reverse transcriptase telomerase is responsible for telomere GT-strand elongation. However, in telomerase-negative cells, low-frequency recombination mechanisms can avert lethality by elongating critically short telomeres. This study focuses on the involvement of the budding yeast Mre11 in telomere recombination and homeostasis. We have identified a novel allele of MRE11, mre11-A470T, that, in telomerase-positive cells, confers a semidominant decrease in telomere size and a recessive defect in telomere healing. In addition, mutant cells lack normal telomere size homeostasis. Telomerase-negative mre11-A470T cells display a Rad51-dependent bypass of replicative senescence via induction of a highly efficient type I-related recombination pathway termed type IA. The type IA pathway involves an amplification of subtelomeric Y' elements, coupled with elongated and more heterogeneous telomere tracts relative to the short telomere size of type I survivors. The data have led us to propose the involvement of break-induced replication in telomere expansion. The differing phenotypes elicited by the mre11-A470T mutants in telomerase-positive and telomerase-negative cells have also led us to speculate that the telomere end structure may be modified differentially in mre11-A470T cells, directing the telomere into specific pathways. |
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Authors:
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Immanual S Joseph; Alpana Kumari; Mrinal K Bhattacharyya; Honghai Gao; Bibo Li; Arthur J Lustig |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-04-26 |
Journal Detail:
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Title: Genetics Volume: 185 ISSN: 1943-2631 ISO Abbreviation: Genetics Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-27 Completed Date: 2010-11-16 Revised Date: 2011-07-19 |
Medline Journal Info:
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Nlm Unique ID: 0374636 Medline TA: Genetics Country: United States |
Other Details:
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Languages: eng Pagination: 761-70 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, Tulane University Medical Center, New Orleans, Louisiana 70112, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Blotting, Southern Cell Aging* Endodeoxyribonucleases / genetics* Exodeoxyribonucleases / genetics* Mutation / genetics* Rad52 DNA Repair and Recombination Protein / genetics Recombination, Genetic* Saccharomyces cerevisiae / genetics*, growth & development, metabolism Saccharomyces cerevisiae Proteins / genetics* Telomerase / metabolism Telomere / genetics* |
| Grant Support | |
ID/Acronym/Agency:
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R01 GM069943/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/RAD52 protein, S cerevisiae; 0/Rad52 DNA Repair and Recombination Protein; 0/Saccharomyces cerevisiae Proteins; EC 2.7.7.49/Telomerase; EC 3.1.-/Endodeoxyribonucleases; EC 3.1.-/Exodeoxyribonucleases; EC 3.1.-/MRE11 protein, S cerevisiae |
| Comments/Corrections | |
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