Multi-disciplinary research

EXO1-dependent single-stranded DNA at telomeres activates subsets of DNA damage and spindle checkpoint pathways in budding yeast yku70Δ mutants (2002)

Author(s): Maringele L; Lydall D

    Abstract: We have examined the role of checkpoint pathways in responding to a yku70Delta defect in budding yeast. We show that CHK1, MEC1, and RAD9 checkpoint genes are required for efficient cell cycle arrest of yku70Delta mutants cultured at 37 degrees C, whereas RAD17, RAD24, MEC3, DDC1, and DUN1 play insignificant roles. We establish that cell cycle arrest of yku70Delta mutants is associated with increasing levels of single-stranded DNA in subtelomeric Y' regions, and find that the mismatch repair-associated EXO1 gene is required for both ssDNA generation and cell cycle arrest of yku70Delta mutants. In contrast, MRE11 is not required for ssDNA generation. The behavior of yku70Delta exo1Delta double mutants strongly indicates that ssDNA is an important component of the arrest signal in yku70Delta mutants and demonstrates a link between damaged telomeres and mismatch repair-associated exonucleases. This link is confirmed by our demonstration that EXO1 also plays a role in ssDNA generation in cdc13-1 mutants. We have also found that the MAD2 but not the BUB2 spindle checkpoint gene is required for efficient arrest of yku70Delta mutants. Therefore, subsets of both DNA-damage and spindle checkpoint pathways cooperate to regulate cell division of yku70Delta mutants.

      • Date: 01-08-2002
      • Journal: Genes & Development
      • Volume: 16
      • Issue: 15
      • Pages: 1919-1933
      • Publisher: Cold Spring Harbor Laboratory Press
      • Publication type: Article
      • Bibliographic status: Published

      Keywords: *Antigens, Nuclear Base Pair Mismatch Calcium-Binding Proteins/physiology Cell Cycle/genetics/*physiology Cell Cycle Proteins/physiology Comparative Study *DNA Damage *DNA Repair DNA, Fungal/*genetics DNA, Single-Stranded/*genetics/metabolism DNA-Binding Proteins/chemistry/deficiency/genetics/*physiology Dimerization Exodeoxyribonucleases/*physiology Fungal Proteins/physiology *Genes, cdc Nuclear Proteins/chemistry/deficiency/genetics/*physiology Protein Kinases/physiology Saccharomyces cerevisiae/cytology/*genetics Saccharomyces cerevisiae Proteins/chemistry/genetics/*physiology Sequence Deletion Support, Non-U.S. Gov't Telomere/*metabolism


      Dr Laura Maringele
      Wellcome Trust CD Fellow