Drosophila Ctf4 is essential for efficient DNA replication and normal cell cycle progression.
Drosophila Ctf4 is essential for efficient DNA replication and normal cell cycle progression.
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DOI：
10.1186/1471-2199-12-13
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发表时间：
2011-04-06
影响因子：
--
通讯作者：
Christensen TW
中科院分区：
文献类型：
--
作者：
Gosnell JA;Christensen TW
正确协调DNA复制叉的功能对细胞的正常功能至关重要。具体来说，解旋酶和聚合酶活性的精确协调对于有效通过S期至关重要。Ctf4蛋白已被证明是复制叉的中心成员，连接复制MCM解旋酶和DNA聚合酶α引物酶。此外，它还被认为是促进复制叉稳定性的复合体——叉保护复合体（FPC）的一员，对姐妹染色单体内聚也很重要。因此，了解Ctf4在多细胞生物背景下的作用将是我们理解其在发育和疾病过程中潜在作用的组成部分。我们发现果蝇Ctf4是一种保守蛋白，它与GINS复合物、Mcm2和聚合酶α引物酶的成员相互作用。在果蝇体内使用RNAi敲除CTF4，我们发现CTF4是生存能力、S期进展、姐妹染色单体内聚、内复制和应对复制应激所必需的。Ctf4仍然是DNA复制的核心角色。我们的发现与之前报道的CTF4在酵母、爪蟾提取物和人类组织培养中的功能一致。我们发现Ctf4的功能是保守的，果蝇可以有效地作为模型来进一步探索Ctf4作为复制叉成员的精确功能及其在发育中的可能作用。
Proper coordination of the functions at the DNA replication fork is vital to the normal functioning of a cell. Specifically the precise coordination of helicase and polymerase activity is crucial for efficient passage though S phase. The Ctf4 protein has been shown to be a central member of the replication fork and links the replicative MCM helicase and DNA polymerase α primase. In addition, it has been implicated as a member of a complex that promotes replication fork stability, the Fork Protection Complex (FPC), and as being important for sister chromatid cohesion. As such, understanding the role of Ctf4 within the context of a multicellular organism will be integral to our understanding of its potential role in developmental and disease processes. We find that Drosophila Ctf4 is a conserved protein that interacts with members of the GINS complex, Mcm2, and Polymerase α primase. Using in vivo RNAi knockdown of CTF4 in Drosophila we show that Ctf4 is required for viability, S phase progression, sister chromatid cohesion, endoreplication, and coping with replication stress. Ctf4 remains a central player in DNA replication. Our findings are consistent with what has been previously reported for CTF4 function in yeast, Xenopus extracts, and human tissue culture. We show that Ctf4 function is conserved and that Drosophila can be effectively used as a model to further probe the precise function of Ctf4 as a member of the replication fork and possible roles in development.
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影响因子：
4
作者：
Leman, Adam R.;Noguchi, Chiaki;Noguchi, Eishi
通讯作者：
Noguchi, Eishi
DOI：
10.1073/pnas.0805189105
发表时间：
2008-08-26
影响因子：
11.1
作者：
Park, So Young;Asano, Maki
通讯作者：
Asano, Maki
影响因子：
4.8
作者：
Bermudez, Vladimir P.;Farina, Andrea;Hurwitz, Jerard
通讯作者：
Hurwitz, Jerard
影响因子：
14.9
作者：
Marchler-Bauer A;Anderson JB;Chitsaz F;Derbyshire MK;DeWeese-Scott C;Fong JH;Geer LY;Geer RC;Gonzales NR;Gwadz M;He S;Hurwitz DI;Jackson JD;Ke Z;Lanczycki CJ;Liebert CA;Liu C;Lu F;Lu S;Marchler GH;Mullokandov M;Song JS;Tasneem A;Thanki N;Yamashita RA;Zhang D;Zhang N;Bryant SH
通讯作者：
Bryant SH
影响因子：
3.3
作者：
Apger, Jennifer;Reubens, Michael;Christensen, Tim W.
通讯作者：
Christensen, Tim W.