Repair of UV-induced DNA lesions in natural Saccharomyces cerevisiae telomeres is moderated by Sir2 and Sir3, and inhibited by yKu-Sir4 interaction

Nucleic Acids Res. 2017 May 5;45(8):4577-4589. doi: 10.1093/nar/gkx123.

Abstract

Ultraviolet light (UV) causes DNA damage that is removed by nucleotide excision repair (NER). UV-induced DNA lesions must be recognized and repaired in nucleosomal DNA, higher order structures of chromatin and within different nuclear sub-compartments. Telomeric DNA is made of short tandem repeats located at the ends of chromosomes and their maintenance is critical to prevent genome instability. In Saccharomyces cerevisiae the chromatin structure of natural telomeres is distinctive and contingent to telomeric DNA sequences. Namely, nucleosomes and Sir proteins form the heterochromatin like structure of X-type telomeres, whereas a more open conformation is present at Y'-type telomeres. It is proposed that there are no nucleosomes on the most distal telomeric repeat DNA, which is bound by a complex of proteins and folded into higher order structure. How these structures affect NER is poorly understood. Our data indicate that the X-type, but not the Y'-type, sub-telomeric chromatin modulates NER, a consequence of Sir protein-dependent nucleosome stability. The telomere terminal complex also prevents NER, however, this effect is largely dependent on the yKu-Sir4 interaction, but Sir2 and Sir3 independent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Damage
  • DNA Repair*
  • DNA, Fungal / genetics
  • DNA, Fungal / metabolism
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Kinetics
  • Nucleosomes / chemistry
  • Nucleosomes / metabolism
  • Protein Binding
  • Protein Folding
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae / radiation effects*
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae / genetics*
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae / metabolism
  • Sirtuin 2 / genetics*
  • Sirtuin 2 / metabolism
  • Telomere / chemistry
  • Telomere / metabolism
  • Telomere / radiation effects*
  • Ultraviolet Rays

Substances

  • DNA, Fungal
  • DNA-Binding Proteins
  • Nucleosomes
  • SIR3 protein, S cerevisiae
  • SIR4 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae
  • YKU70 protein, S cerevisiae
  • SIR2 protein, S cerevisiae
  • Sirtuin 2

Grant support