Relative contribution of four nucleases, CtIP, Dna2, Exo1 and Mre11, to the initial step of DNA double-strand break repair by homologous recombination in both the chicken DT40 and human TK6 cell lines.
Relative contribution of four nucleases, CtIP, Dna2, Exo1 and Mre11, to the initial step of DNA double-strand break repair by homologous recombination in both the chicken DT40 and human TK6 cell lines.
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在Chicken DT40和Human TK6细胞系中，通过同源重组的DNA双链破裂修复的初始步骤，四个核酸酶CTIP，DNA2，EXO1和MRE11的相对贡献对DNA双链破裂修复的第一步。
DOI：
10.1111/gtc.12310
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Sasanuma H
中科院分区：
文献类型：
--
作者：
Hoa NN;Akagawa R;Yamasaki T;Hirota K;Sasa K;Natsume T;Kobayashi J;Sakuma T;Yamamoto T;Komatsu K;Kanemaki MT;Pommier Y;Takeda S;Sasanuma H
同源重组（Homologous recombination， HR）是由双链断裂（double-strand break， DSB）切除引发的，在此过程中DSB被核酸酶加工生成3'单链DNA。DSB的切除由CtIP和Mre11启动，然后由酿酒酵母中的Dna2和Exo1远程切除。为了分析四种核酸酶CtIP、Mre11、Dna2和Exo1对DSB切除的相对贡献，我们破坏了鸡DT40细胞中编码这些核酸酶的基因。切除DSB需要CtIP和Dna2，而即使在没有Dna2的情况下，Exo1也是必不可少的，这与观察结果一致，Exo1缺陷小鼠没有发育缺陷。尽管Mre11在酿酒酵母的DSB切除中起着关键作用，但Mre11的缺失仅轻微损害DT40细胞的DSB切除。为了进一步测试CtIP和Mre11在其他物种中的作用，我们在人TK6 B细胞系中有条件地破坏CtIP和Mre11基因。与DT40细胞一样，在TK6细胞中，CtIP比Mre11更显著地促进DSB切除。考虑到Mre11在HR中的关键作用，本研究提示Mre11参与了DSB切除以外的机制。综上所述，CtIP和Dna2足以切除DSB，确保HR有效修复DSB。
Homologous recombination (HR) is initiated by double-strand break (DSB) resection, during which DSBs are processed by nucleases to generate 3' single-strand DNA. DSB resection is initiated by CtIP and Mre11 followed by long-range resection by Dna2 and Exo1 in Saccharomyces cerevisiae. To analyze the relative contribution of four nucleases, CtIP, Mre11, Dna2 and Exo1, to DSB resection, we disrupted genes encoding these nucleases in chicken DT40 cells. CtIP and Dna2 are required for DSB resection, whereas Exo1 is dispensable even in the absence of Dna2, which observation agrees with no developmental defect in Exo1-deficient mice. Despite the critical role of Mre11 in DSB resection in S. cerevisiae, loss of Mre11 only modestly impairs DSB resection in DT40 cells. To further test the role of CtIP and Mre11 in other species, we conditionally disrupted CtIP and MRE11 genes in the human TK6 B cell line. As with DT40 cells, CtIP contributes to DSB resection considerably more significantly than Mre11 in TK6 cells. Considering the critical role of Mre11 in HR, this study suggests that Mre11 is involved in a mechanism other than DSB resection. In summary, CtIP and Dna2 are sufficient for DSB resection to ensure efficient DSB repair by HR.
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影响因子：
3.7
作者：
Hoa NN;Kobayashi J;Omura M;Hirakawa M;Yang SH;Komatsu K;Paull TT;Takeda S;Sasanuma H
通讯作者：
Sasanuma H
影响因子：
64.5
作者：
Buis J;Wu Y;Deng Y;Leddon J;Westfield G;Eckersdorff M;Sekiguchi JM;Chang S;Ferguson DO
通讯作者：
Ferguson DO
DOI：
10.1083/jcb.201401146
发表时间：
2014-09-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Barton O;Naumann SC;Diemer-Biehs R;Künzel J;Steinlage M;Conrad S;Makharashvili N;Wang J;Feng L;Lopez BS;Paull TT;Chen J;Jeggo PA;Löbrich M
通讯作者：
Löbrich M
DOI：
10.1073/pnas.121075598
发表时间：
2001-07-17
影响因子：
11.1
作者：
Debrauwère, H;Loeillet, S;Nicolas, A
通讯作者：
Nicolas, A
影响因子：
8
作者：
Imamura, O;Fujita, K;Matsumoto, T
通讯作者：
Matsumoto, T