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KEOPS Complex Promotes Homologous Recombination Via DNA Resection

Overview
Specialty Biochemistry
Date 2019 Apr 3
PMID 30937455
Citations 15
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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.

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References
1.
Mao D, Neculai D, Downey M, Orlicky S, Haffani Y, Ceccarelli D . Atomic structure of the KEOPS complex: an ancient protein kinase-containing molecular machine. Mol Cell. 2008; 32(2):259-75. PMC: 3098719. DOI: 10.1016/j.molcel.2008.10.002. View

2.
Zubko M, Guillard S, Lydall D . Exo1 and Rad24 differentially regulate generation of ssDNA at telomeres of Saccharomyces cerevisiae cdc13-1 mutants. Genetics. 2004; 168(1):103-15. PMC: 1448105. DOI: 10.1534/genetics.104.027904. View

3.
Jasin M, Rothstein R . Repair of strand breaks by homologous recombination. Cold Spring Harb Perspect Biol. 2013; 5(11):a012740. PMC: 3809576. DOI: 10.1101/cshperspect.a012740. View

4.
Silberman R, Kupiec M . Plasmid-mediated induction of recombination in yeast. Genetics. 1994; 137(1):41-8. PMC: 1205951. DOI: 10.1093/genetics/137.1.41. View

5.
Fu X, Duan Y, Liu Y, Cai C, Meng F, Zhou J . Telomere recombination preferentially occurs at short telomeres in telomerase-null type II survivors. PLoS One. 2014; 9(3):e90644. PMC: 3940914. DOI: 10.1371/journal.pone.0090644. View