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

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390085/
• 关键词: chromatin; CAF-1; nucleosome; DNA replication; chromatin replication; epigenetics; DNA複製; クロマチン複製; ヌクレオソーム; ヌクレオソームアセンブリー; ヒストン; ジーンターゲティング; 細胞記憶; DDM1; モノユビキチン化

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

新复制的DNA在复制叉通过后不久组装成核小体。核小体的这种快速形成在功能上与DNA复制相关，并且对于维持增殖细胞中的基因组完整性起关键作用（Shibahara和Stillman，Cell，1999）。最近，我们利用CAF-1缺陷的鸡DT 40细胞系，发现在体内没有CAF-1和/或ASF 1功能的情况下，S期进程被延迟，DNA复制过程中的快速核小体组装被干扰。（Sanematsu等人，J.Biol.Chem.，2006年）。这是CAF-1和ASF 1参与体内DNA复制过程中快速核小体组装的第一个直接证据。此外，我们获得了一些有趣的证据，证明在用HU处理后CAF-1参与Chk 1依赖性检查点途径（Takami等人， ...更多信息 拟南芥中caf-1（fas）的功能丧失突变体显示出两个分生组织的严重干扰的细胞和功能组织（卡亚等人，Cell，2001）。我们还表明，内源性CACTA转座子的转录基因沉默（TGS）在fas突变体中以随机方式很少释放，而不降低DNA甲基化。其他内源性沉默基因在不同的染色体位点也转录激活非伴随彼此。此外，沉默转基因β-葡糖醛酸糖苷酶（GUS）的TGS也在fas突变体中随机去阻遏，与发育异常无关，并且GUS的活化状态在生长期间维持以产生表达GUS的细胞簇（Ono等人，Genes Cells，2006）。两者合计，我们强烈建议，CAF-1确保通过多轮细胞分裂的表观遗传状态的稳定维护，CAF-1功能的缺陷解释了Fas突变体中各种表型的随机发生。少

项目成果

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。

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

Chromatin assembly is required for rapid nucleosome formation during DNA replication and efficient Chk1 activation in vertebrate chicken DT40 cells.

脊椎动物鸡 DT40 细胞中 DNA 复制过程中的快速核小体形成和 Chk1 的有效激活需要染色质组装。

• 发表时间: 2007
• 期刊: Mol. Biol. Cell. 18(1)
• 作者: Takami;Y.;Ono;T.;Fukagawa;T.;K-i;Shibahara;T.Nakayama.
• 通讯作者: T.Nakayama.

Enhanced homologous recombination and T-DNA integration in chromatin assemble 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。

• 发表时间: 2006
• 期刊: EMBO J. 25(23)
• 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.

DNA複製・DNA修復がわかる「DNA修復とヌクレオチド除去修復

解释DNA复制和DNA修复的“DNA修复和核苷酸切除修复”

• 发表时间: 2004
• 作者: 久保知大;柴原慶一
• 通讯作者: 柴原慶一