KEOPS complex promotes homologous recombination via DNA resection

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• The KEOPS complex is crucial for telomere maintenance and tRNA modification in eukaryotes.
• Its role in DNA repair pathways remains largely unexplored.

Purpose of the Study:

• To investigate the potential involvement of the KEOPS complex in DNA damage response and repair.
• To elucidate the mechanism by which KEOPS might influence DNA repair processes.

Main Methods:

• Assessing DNA damage response and homologous recombination in yeast strains with altered KEOPS function.
• In vitro DNA binding assays and in vivo chromatin recruitment studies of KEOPS.
• Investigating the interaction of KEOPS with key DNA repair factors like Exo1, Dna2, and the MRX complex.

Main Results:

• KEOPS complex positively regulates DNA damage response and homologous recombination, independent of its tRNA modification activity.
• KEOPS exhibits direct DNA binding activity and is recruited to DNA break sites.
• KEOPS promotes DNA end resection by facilitating Exo1 and Dna2 recruitment to breaks.
• Synergistic defects in resection observed upon combined inactivation of KEOPS and MRX complexes indicate functional redundancy.

Conclusions:

• The KEOPS complex has a novel, t6A-independent function in DNA double-strand break (DSB) repair, specifically in promoting DNA resection.
• KEOPS may function as a DSB sensor, contributing to the maintenance of genomic stability.