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The fission yeast MRN complex tethers dysfunctional telomeres for NHEJ repair
Author(s) -
Reis Clara Correia,
Batista Sílvia,
Ferreira Miguel Godinho
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2012.313
Subject(s) - biology , telomere , dna repair , schizosaccharomyces pombe , fission , schizosaccharomyces , genetics , homologous recombination , yeast , dna , saccharomyces cerevisiae , physics , quantum mechanics , neutron
Telomeres protect the natural ends of chromosomes from being repaired as deleterious DNA breaks. In fission yeast, absence of Taz1 (homologue of human TRF1 and TRF2) renders telomeres vulnerable to DNA repair. During the G1 phase, when non‐homologous end joining (NHEJ) is upregulated, taz1 Δ cells undergo telomere fusions with consequent loss of viability. Here, we show that disruption of the fission yeast MRN (Rad23 MRE11 ‐Rad50‐Nbs1) complex prevents NHEJ at telomeres and, as a result, rescues taz1 Δ lethality in G1. Neither Tel1 ATM activation nor 5′‐end resection was required for telomere fusion. Nuclease activity of Rad32 MRE11 was also dispensable for NHEJ. Mutants unable to coordinate metal ions required for nuclease activity were proficient in NHEJ repair. In contrast, Rad32 MRE11 mutations that affect binding and/or positioning of DNA ends leaving the nuclease function largely unaffected also impaired NHEJ at telomeres and restored the viability of taz1 Δ in G1. Consistently, MRN structural integrity but not nuclease function is also required for NHEJ of independent DNA ends in a novel split‐molecule plasmid assay. Thus, MRN acts to tether unlinked DNA ends, allowing for efficient NHEJ.