MCM8IP activates the MCM8-9 helicase to promote DNA synthesis and homologous recombination upon DNA damage

Nat Commun. 2020 Jun 11;11(1):2948. doi: 10.1038/s41467-020-16718-3.


Homologous recombination (HR) mediates the error-free repair of DNA double-strand breaks to maintain genomic stability. Here we characterize C17orf53/MCM8IP, an OB-fold containing protein that binds ssDNA, as a DNA repair factor involved in HR. MCM8IP-deficient cells exhibit HR defects, especially in long-tract gene conversion, occurring downstream of RAD51 loading, consistent with a role for MCM8IP in HR-dependent DNA synthesis. Moreover, loss of MCM8IP confers cellular sensitivity to crosslinking agents and PARP inhibition. Importantly, we report that MCM8IP directly associates with MCM8-9, a helicase complex mutated in primary ovarian insufficiency, and RPA1. We additionally show that the interactions of MCM8IP with MCM8-9 and RPA facilitate HR and promote replication fork progression and cellular viability in response to treatment with crosslinking agents. Mechanistically, MCM8IP stimulates the helicase activity of MCM8-9. Collectively, our work identifies MCM8IP as a key regulator of MCM8-9-dependent DNA synthesis during DNA recombination and replication.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Survival / genetics
  • Chromatin / genetics
  • Chromatin / metabolism
  • DNA Damage*
  • DNA Replication*
  • DNA, Single-Stranded / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • HCT116 Cells
  • HEK293 Cells
  • Humans
  • Minichromosome Maintenance Proteins / genetics
  • Minichromosome Maintenance Proteins / metabolism*
  • Mutation
  • Protein Binding
  • Rad51 Recombinase / metabolism
  • Recombinational DNA Repair*
  • Replication Protein A / genetics
  • Replication Protein A / metabolism


  • Chromatin
  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • HROB protein, human
  • RPA1 protein, human
  • Replication Protein A
  • Rad51 Recombinase
  • MCM8 protein, human
  • MCM9 protein, human
  • Minichromosome Maintenance Proteins