Chromatin replication through cellular proliferation in eukaryotic cells

真核细胞中通过细胞增殖进行染色质复制

基本信息

批准号：
16390085
负责人：
SHIBAHARA Kei-ichi
金额：
$ 9.09万
依托单位：
National Institute of Genetics
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

A newly replicated DNA is assembled into nucleosome soon after the passage of replication fork. This rapid formation of nucleosome is functionally linked to DNA replication and plays a critical role for the maintenance of genome integrity in proliferating cells (Shibahara and Stillman, Cell, 1999). Two histone-binding proteins, CAF-1 and ASF1, are assumed to be involved in some process of this replication-coupled nucleosome assembly reaction.Using CAF-1-deficient chicken DT40 cell lines, we had recently shown that without CAF-1 and/or ASF1 function, S-phase progression was delayed and a rapid nucleosome assembly during DNA replication was disturbed in vivo. (Sanematsu, et al., J.Biol.Chem., 2006). This is the first direct evidence for the involvement of CAF-1 and ASF1 in a rapid nucleosome assembly during DNA replication in vivo. In addition, we obtained some interesting evidence for that CAF-1 is involved in Chk1-dependent checkpoint pathway after the treatment with HU (Takami et al., … More Mol.Biol.Cell, 2007).The loss-of-function mutants of caf-1 (fas) in Arabidopsis displayed severely disturbed cellular and functional organization of both meristems (Kaya et al., Cell, 2001). We also had shown that transcriptional gene silencing (TGS) of endogenous CACTA transposons was released infrequently in a stochastic manner in fas mutants without decreasing DNA methylation. Other endogenous silent genes at different chromosomal sites were also transcriptionally activated non-concomitantly with each other. Furthermore, TGS of the silent transgene β-glucuronidase (GUS) was also de-repressed randomly in fas mutants, irrespectively of developmental abnormalities, and the activated state of GUS was maintained during growth to produce clusters of cells expressing GUS (Ono et al., Genes Cells, 2006). Taken together, we strongly suggest that CAF-1 ensures stable maintenance of epigenetic states through multiple rounds of cell divisions and that defects in CAF-1 functions explain the stochastic occurrence of various phenotypes in the fas mutants. Less

复制叉通过后不久，将新复制的DNA组装成核小体。核小体的这种快速形成在功能上与DNA复制有关，并在维持基因组完整性中在增殖细胞中起关键作用（Shibahara和Stillman，Cell，1999）。 Two histone-binding proteins, CAF-1 and ASF1, are assumed to be involved in some process of this replication-coupled nucleosome assembly reaction.Using CAF-1-deficiency chicken DT40 cell lines, we had recently shown that without CAF-1 and/or ASF1 function, S-phase progression was delayed and a rapid nuclear nucleosome assembly during DNA replication was disturbed in vivo. （Sanematsu等人，J.Biol.Chem。，2006）。这是在体内DNA复制过程中CAF-1和ASF1参与快速核核小体组装中的第一个直接证据。此外，我们获得了一些有趣的证据，证明CAF-1与HU处理后有关CHK1依赖性检查点途径（Takami等人，…Mor.biol.Cell，2007年）。拟南芥中CAF-1（FAS）的功能丧失突变体显示出严重影响的两个分生组织的细胞和功能组织（Kaya等，Cell，2001）。我们还表明，内源性仙人掌转座子的转录基因沉默（TGS）在FAS突变体中很少以随机方式释放，而不会降低DNA甲基化。在不同染色体部位的其他内源性沉默基因也彼此转录非激活。此外，在FAS突变体中随机去压缩了沉默的转基因β-葡萄糖醛酸苷酶（GUS）的TGS，无论发生异常，并且在生长过程中保持活化的GUS状态以产生表达GUS GUS的细胞的簇（Ono等人，Genes Cell。，Genes Cell。，基因，2006）。综上所述，我们强烈建议CAF-1通过多轮细胞分裂确保表观遗传状态的稳定维持，并且CAF-1功能中的缺陷解释了FAS突变体中各种表型的随机发生。较少的

项目成果

期刊论文数量（38）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Enhanced homologous recombination and T-DNA integration in chromatin assembly factor-I mutants in Arabidopsis thaliana.

拟南芥染色质组装因子-I 突变体中同源重组和 T-DNA 整合增强。

DOI：
发表时间：
2006
期刊：
EMBO J. 25(23)
影响因子：
0
作者：
Endo;M.
通讯作者：
M.

Chromatin assembly factor 1 ensures the stable maintenance of silent chromatin states in Arabidopsis

DOI：
10.1111/j.1365-2443.2006.00928.x
发表时间：
2006-02-01
期刊：
GENES TO CELLS
影响因子：
2.1
作者：
Ono, T;Kaya, H;Shibahara, K
通讯作者：
Shibahara, K

Histone acetyltransferase I is dispensable for replication-coupled chromatin assembly but contributes to recover DNA damages created following replication blockage in vertebrate cells.

组蛋白乙酰转移酶 I 对于复制偶联染色质组装来说是可有可无的，但有助于恢复脊椎动物细胞中复制受阻后产生的 DNA 损伤。

DOI：
发表时间：
2006
期刊：
Biochem Biophys Res Commun 345
影响因子：
0
作者：
Barman;HK.;Takami;Y.;Ono T.;Nishijima;H.;Sanematsu;F.;Shibahara;K-i.;Nakayama;T.
通讯作者：
T.

Enhanced homologous recombination and T-DNA integration in chromatin assembly factor-1 mutants in Arabidopsis thaliana.

拟南芥染色质组装因子 1 突变体中同源重组和 T-DNA 整合增强。

DOI：
发表时间：
2006
期刊：
EMBO J. 25(23)
影响因子：
0
作者：
Endo;M.;Ishikawa;Y.;Kaya;H.;Araki;T.;Shibahara;K-i.;Ito;Y.;Osakabe;K.;Abe;K.;Ichikawa;H.;Valentine;L.;Hohn;B.;Toki;S.
通讯作者：
S.

遺伝子導入方法、ジーンターゲッティング方法及びトランスジェニック植物の製造方法

基因导入方法、基因打靶方法以及转基因植物的制造方法