title: An mre11 mutation that promotes telomere recombination and an efficient bypass of senescence.
abstract: 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.
authors.affiliation: Department of Biochemistry, Tulane University Medical Center, New Orleans, Louisiana 70112, USA.
authors.forename: Immanual S
authors.initials: IS
authors.lastname: Joseph
authors.forename: Alpana
authors.initials: A
authors.lastname: Kumari
authors.forename: Mrinal K
authors.initials: MK
authors.lastname: Bhattacharyya
authors.forename: Honghai
authors.initials: H
authors.lastname: Gao
authors.forename: Bibo
authors.initials: B
authors.lastname: Li
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Lustig
mesh_terms: D015139:Blotting, Southern; D016922:Cellular Senescence; D004706:Endodeoxyribonucleases / Q000235:genetics*; D005090:Exodeoxyribonucleases / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D051721:Rad52 DNA Repair and Recombination Protein / Q000235:genetics; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000235:genetics*
chemical_list: C497197:RAD52 protein, S cerevisiae; D051721:Rad52 DNA Repair and Recombination Protein; D029701:Saccharomyces cerevisiae Proteins; D019098:Telomerase; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; C094191:MRE11 protein, S cerevisiae