1. KEOPS complex promotes homologous recombination via DNA resection.
- Author
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He MH, Liu JC, Lu YS, Wu ZJ, Liu YY, Wu Z, Peng J, and Zhou JQ
- Subjects
- Binding, Competitive, Chromatin chemistry, DNA chemistry, DNA Breaks, Double-Stranded, DNA Repair, DNA-Binding Proteins metabolism, Endodeoxyribonucleases metabolism, Exodeoxyribonucleases metabolism, Metalloendopeptidases metabolism, Mutation, Protein Binding, Protein Serine-Threonine Kinases metabolism, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae Proteins metabolism, Telomere metabolism, Transcription Factors metabolism, DNA Helicases physiology, DNA, Fungal, Exodeoxyribonucleases physiology, Homologous Recombination, Recombinational DNA Repair, Saccharomyces cerevisiae Proteins physiology
- Abstract
KEOPS complex is one of the most conserved protein complexes in eukaryotes. It plays important roles in both telomere uncapping and tRNA N6-threonylcarbamoyladenosine (t6A) modification in budding yeast. But whether KEOPS complex plays any roles in DNA repair remains unknown. Here, we show that KEOPS complex plays positive roles in both DNA damage response and homologous recombination-mediated DNA repair independently of its t6A synthesis function. Additionally, KEOPS displays DNA binding activity in vitro, and is recruited to the chromatin at DNA breaks in vivo, suggesting a direct role of KEOPS in DSB repair. Mechanistically, KEOPS complex appears to promote DNA end resection through facilitating the association of Exo1 and Dna2 with DNA breaks. Interestingly, inactivation of both KEOPS and Mre11/Rad50/Xrs2 (MRX) complexes results in synergistic defect in DNA resection, revealing that KEOPS and MRX have some redundant functions in DNA resection. Thus we uncover a t6A-independent role of KEOPS complex in DNA resection, and propose that KEOPS might be a DSB sensor to assist cells in maintaining chromosome stability., (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2019
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