Department of Radiation and Cellular Oncology/Department of Molecular Genetics and Cell Biology, University of Chicago, 920 E 58th Street, CLSC 817, Chicago, IL 60637, USA.
Genetics. 2024 Sep 4;228(1). doi: 10.1093/genetics/iyae112.
The conserved Rad2/XPG family 5'-3' exonuclease, exonuclease 1 (Exo1), plays many roles in DNA metabolism including during resolution of DNA double-strand breaks via homologous recombination. Prior studies provided evidence that the end resection activity of Exo1 is downregulated in yeast and mammals by Cdk1/2 family cyclin-dependent and checkpoint kinases, including budding yeast kinase Rad53 which functions in mitotic cells. Here, we provide evidence that the master meiotic kinase Mek1, a paralog of Rad53, limits 5'-3' single-strand resection at the sites of programmed meiotic DNA breaks. Mutational analysis suggests that the mechanism of Exo1 suppression by Mek1 differs from that of Rad53.
保守的 Rad2/XPG 家族 5'-3'外切核酸酶,外切核酸酶 1(Exo1),在 DNA 代谢中发挥着许多作用,包括通过同源重组来解决 DNA 双链断裂。先前的研究提供了证据,表明在酵母和哺乳动物中,Cdk1/2 家族细胞周期蛋白依赖性激酶和检查点激酶,包括在有丝分裂细胞中发挥作用的芽殖酵母激酶 Rad53,下调了 Exo1 的末端切除活性。在这里,我们提供的证据表明,主要的减数分裂激酶 Mek1,Rad53 的同源物,限制了有丝分裂 DNA 断裂部位的 5'-3'单链切除。突变分析表明,Mek1 对 Exo1 的抑制机制与 Rad53 不同。