The Shu complex promotes error-free tolerance of alkylation-induced base excision repair products

Nucleic Acids Res. 2016 Sep 30;44(17):8199-215. doi: 10.1093/nar/gkw535. Epub 2016 Jun 13.


Here, we investigate the role of the budding yeast Shu complex in promoting homologous recombination (HR) upon replication fork damage. We recently found that the Shu complex stimulates Rad51 filament formation during HR through its physical interactions with Rad55-Rad57. Unlike other HR factors, Shu complex mutants are primarily sensitive to replicative stress caused by MMS and not to more direct DNA breaks. Here, we uncover a novel role for the Shu complex in the repair of specific MMS-induced DNA lesions and elucidate the interplay between HR and translesion DNA synthesis. We find that the Shu complex promotes high-fidelity bypass of MMS-induced alkylation damage, such as N3-methyladenine, as well as bypassing the abasic sites generated after Mag1 removes N3-methyladenine lesions. Furthermore, we find that the Shu complex responds to ssDNA breaks generated in cells lacking the abasic site endonucleases. At each lesion, the Shu complex promotes Rad51-dependent HR as the primary repair/tolerance mechanism over error-prone translesion DNA polymerases. Together, our work demonstrates that the Shu complex's promotion of Rad51 pre-synaptic filaments is critical for high-fidelity bypass of multiple replication-blocking lesion.

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / metabolism
  • Alkylation
  • Camptothecin / pharmacology
  • Cisplatin / pharmacology
  • DNA Damage / genetics
  • DNA Polymerase beta / metabolism
  • DNA Repair* / drug effects
  • DNA, Fungal / biosynthesis
  • Epistasis, Genetic / drug effects
  • Etoposide / pharmacology
  • Genes, Fungal
  • Genetic Loci
  • Homologous Recombination / genetics
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Hydroxyurea / pharmacology
  • Methyl Methanesulfonate / pharmacology
  • Models, Biological
  • Mutation / genetics
  • Mutation Rate
  • Protein Binding / drug effects
  • Radiation, Ionizing
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae / radiation effects
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Ultraviolet Rays


  • DNA, Fungal
  • N3-methyladenine
  • Saccharomyces cerevisiae Proteins
  • Etoposide
  • Methyl Methanesulfonate
  • Hydrogen Peroxide
  • DNA Polymerase beta
  • Adenine
  • Cisplatin
  • Hydroxyurea
  • Camptothecin