Differential suppression of DNA repair deficiencies of Yeast rad50, mre11 and xrs2 mutants by EXO1 and TLC1 (the RNA component of telomerase).
Differential suppression of DNA repair deficiencies of Yeast rad50, mre11 and xrs2 mutants by EXO1 and TLC1 (the RNA component of telomerase).
复制标题
EXO1 和 TLC1（端粒酶的 RNA 成分）对酵母 rad50、mre11 和 xrs2 突变体 DNA 修复缺陷的差异抑制。
DOI：
10.1093/genetics/160.1.49
复制
发表时间：
2002
期刊：
影响因子：
3.3
通讯作者：
Resnick,MichaelA
中科院分区：
文献类型：
--
作者：
Lewis,LKevin;Karthikeyan,G;Westmoreland,JamesW;Resnick,MichaelA
Rad50, Mre11, and Xrs2 form a nuclease complex that functions in both nonhomologous end-joining (NHEJ) and recombinational repair of DNA double-strand breaks (DSBs). A search for highly expressed cDNAs that suppress the DNA repair deficiency ofrad50mutants yielded multiple isolates of two genes:EXO1andTLC1. Overexpression ofEXO1orTLC1increased the resistance ofrad50, mre11, andxrs2mutants to ionizing radiation and MMS, but did not increase resistance in strains defective in recombination (rad51, rad52, rad54, rad59) or NHEJ only (yku70, sir4). Increased Exo1 orTLC1RNA did not alter checkpoint responses or restore NHEJ proficiency, but DNA repair defects ofyku70andrad27 (fen)mutants were differentially suppressed by the two genes. Overexpression of Exo1, but not mutant proteins containing substitutions in the conserved nuclease domain, increased recombination and suppressed HO andEcoRI endonuclease-induced killing ofrad50strains.exo1 rad50mutants lacking both nuclease activities exhibited a high proportion of enlarged, G2-arrested cells and displayed a synergistic decrease in DSB-induced plasmid:chromosome recombination. These results support a model in which the nuclease activity of the Rad50/Mre11/Xrs2 complex is required for recombinational repair, but not NHEJ. We suggest that the 5′–3′ exo activity of Exo1 is able to substitute for Rad50/Mre11/Xrs2 in rescission of specific classes of DSB end structures. Gene-specific suppression byTLC1, which encodes the RNA subunit of the yeast telomerase complex, demonstrates that components of telomerase can also impact on DSB repair pathways.
