A tale of two tails: activation of DNA damage checkpoint kinase Mec1/ATR by the 9-1-1 clamp and by Dpb11/TopBP1.
A tale of two tails: activation of DNA damage checkpoint kinase Mec1/ATR by the 9-1-1 clamp and by Dpb11/TopBP1.
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DOI：
10.1016/j.dnarep.2009.03.011
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发表时间：
2009-09-02
期刊：
影响因子：
3.8
通讯作者：
Burgers PM
中科院分区：
文献类型：
--
作者：
Navadgi-Patil VM;Burgers PM
DNA损伤和复制检查点激酶Mec 1/ATR是PI 3-激酶相关激酶的成员，其功能响应于各种遗传毒性应激。检测点钳9-1-1（S.粟酒酵母和哺乳动物; cerevisiae）执行两个不同的检查点功能。In S.在酿酒酵母中，DNA结合的9-1-1直接激活Mec 1激酶活性，这是一种在其他生物中尚未证实的功能。9-1-1的第二个保守活性是TopBP 1/Cut 5/Dpb 11募集到停滞的复制位点;随后Mec 1/ATR的激活由TopBP 1/Cut 5/Dpb 11进行。生化研究表明，S. cerevisiae 9-1-1类似于S.酿酒酵母Dpb 11或脊椎动物TopBP 1：激活是由每个激活剂的固有无序的C-末端尾介导的。讨论了Mec 1/ATR多个活化剂的相对贡献。
The DNA damage and replication checkpoint kinase Mec1/ATR is a member of the PI3-kinase related kinases that function in response to various genotoxic stresses. The checkpoint clamp 9-1-1 (Rad9-Rad1-Hus1 in S. pombe and mammals; Ddc1-Rad17-Mec3 in S. cerevisiae) executes two distinct checkpoint functions. In S. cerevisiae, DNA-bound 9-1-1 directly activates Mec1 kinase activity, a function that has not been demonstrated in other organisms. A second, conserved activity of 9-1-1 is that of TopBP1/Cut5/Dpb11 recruitment to stalled replication sites; subsequent activation of Mec1/ATR is carried out by TopBP1/Cut5/Dpb11. Biochemical studies indicate that the mode of Mec1/ATR activation by S. cerevisiae 9-1-1 is analogous to activation by S. cerevisiae Dpb11 or by vertebrate TopBP1: activation is mediated by the intrinsically disordered C-terminal tail of each activator. The relative contributions made by multiple activators of Mec1/ATR are discussed.
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DOI：
10.1073/pnas.1434308100
发表时间：
2003-09-02
影响因子：
11.1
作者：
Bermudez, VP;Maniwa, Y;Hurwitz, J
通讯作者：
Hurwitz, J
影响因子：
4.8
作者：
Burtelow, MA;Roos-Mattjus, PMK;Karnitz, LM
通讯作者：
Karnitz, LM
影响因子：
21.3
作者：
Gambus, A;Jones, RC;Labib, K
通讯作者：
Labib, K
影响因子：
5.3
作者：
Aylon, Y;Kupiec, M
通讯作者：
Kupiec, M
影响因子：
10.5
作者：
Furuya, K;Poitelea, M;Carr, AM
通讯作者：
Carr, AM