Mrc1, a non-essential DNA replication protein, is required for telomere end protection following loss of capping by Cdc13, Yku or telomerase.
Proteins involved in telomere end protection have previously been identified. In Saccharomyces cerevisiae, Cdc13, Yku and telomerase, mainly, prevent telomere uncapping, thus providing telomere stability and avoiding degradation and death by senescence. Here, we report that in the absence of Mrc1, a component of the replication forks, telomeres of cdc13 or yku70 mutants exhibited increased degradation, while telomerase-negative cells displayed accelerated senescence. Moreover, deletion of MRC1 increased the single-strandedness of the telomeres in cdc13-1 and yku70Delta mutant strains. An mrc1 deletion strain also exhibited slight but stable telomere shortening compared to a wild-type strain. Loss of Mrc1's checkpoint function alone did not provoke synthetic growth defects in combination with the cdc13-1 mutation. Combinations between the cdc13-1 mutation and deletion of either TOF1 or PSY2, coding for proteins physically interacting with Mrc1, also resulted in a synthetic growth defect. Thus, the present data suggest that non-essential components of the DNA replication machinery, such as Mrc1 and Tof1, may have a role in telomere stability in addition to their role in fork progression.
Grandin
Nathalie
N
UMR CNRS no 5161, Ecole Normale Supérieure de Lyon, IFR128 BioSciences Gerland, 46, allée d'Italie, 69364 Lyon, France.
Charbonneau
Michel
M
D018797:Cell Cycle Proteins / Q000378:metabolism*; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism*; D017353:Gene Deletion; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000378:metabolism*
C452219:Cdc13 protein, S cerevisiae; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C441579:MRC1 protein, S cerevisiae; D009687:Nuclear Proteins; C494616:Psy2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C119636:TOF1 protein, S cerevisiae; D034501:Telomere-Binding Proteins; C520769:YKU70 protein, S cerevisiae; C081647:high affinity DNA-binding factor, S cerevisiae; D019098:Telomerase