PT  - JOURNAL ARTICLE
AU  - Pal, Sangita
AU  - Postnikoff, Spike D.
AU  - Chavez, Myrriah
AU  - Tyler, Jessica K.
TI  - Impaired cohesion and homologous recombination during replicative aging in budding yeast
AID  - 10.1126/sciadv.aaq0236
DP  - 2018 Feb 01
TA  - Science Advances
PG  - eaaq0236
VI  - 4
IP  - 2
4099  - http://advances.sciencemag.org/content/4/2/eaaq0236.short
4100  - http://advances.sciencemag.org/content/4/2/eaaq0236.full
SO  - Sci Adv2018 Feb 01; 4
AB  - The causal relationship between genomic instability and replicative aging is unclear. We reveal here that genomic instability at the budding yeast ribosomal DNA (rDNA) locus increases during aging, potentially due to the reduced cohesion that we uncovered during aging caused by the reduced abundance of multiple cohesin subunits, promoting increased global chromosomal instability. In agreement, cohesion is lost during aging at other chromosomal locations in addition to the rDNA, including centromeres. The genomic instability in old cells is exacerbated by a defect in DNA double-strand break (DSB) repair that we uncovered in old yeast. This was due to limiting levels of key homologous recombination proteins because overexpression of Rad51 or Mre11 reduced the accumulation of DSBs and largely restored DSB repair in old cells. We propose that increased rDNA instability and the reduced DSB repair capacity of old cells contribute to the progressive accumulation of global chromosomal DNA breaks, where exceeding a threshold of genomic DNA damage ends the replicative life span.