Mrc1 protects uncapped budding yeast telomeres from exonuclease EXO1

DNA Repair (Amst). 2007 Nov;6(11):1607-17. doi: 10.1016/j.dnarep.2007.05.010. Epub 2007 Jul 6.

Abstract

Mrc1 (Mediator of Replication Checkpoint 1) is a component of the DNA replication fork machinery and is necessary for checkpoint activation after replication stress. In this study, we addressed the role of Mrc1 at uncapped telomeres. Our experiments show that Mrc1 contributes to the vitality of both cdc13-1 and yku70Delta telomere capping mutants. Cells with telomere capping defects containing MRC1 or mrc1(AQ), a checkpoint defective allele, exhibit similar growth, suggesting growth defects of cdc13-1 mrc1Delta are not due to checkpoint defects. This is in accordance with Mrc1-independent Rad53 activation after telomere uncapping. Poor growth of cdc13-1 mutants in the absence of Mrc1 is a result of enhanced single stranded DNA accumulation at uncapped telomeres. Consistent with this, deletion of EXO1, encoding a nuclease that contributes to single stranded DNA accumulation after telomere uncapping, improves growth of cdc13-1 mrc1Delta strains and decreases ssDNA production. Our observations show that Mrc1, a core component of the replication fork, plays an important role in telomere capping, protecting from nucleases and checkpoint pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cyclin B / genetics
  • Cyclin B / metabolism
  • DNA, Single-Stranded / metabolism
  • Exodeoxyribonucleases / metabolism*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Mutation
  • Saccharomycetales / enzymology*
  • Saccharomycetales / metabolism
  • Telomere / metabolism*

Substances

  • Cell Cycle Proteins
  • Cyclin B
  • DNA, Single-Stranded
  • Fungal Proteins
  • Exodeoxyribonucleases
  • exodeoxyribonuclease I