BIOCHEM PATHWAYS LINKING DNA REPLICATION & MITOSIS
BIOCHEM PATHWAYS LINKING DNA REPLICATION & MITOSIS
批准号:
6519408
负责人:
john w newport
金额:
$23.94万
依托单位国家:
美国
项目类别:
财政年份:
1991
资助国家:
美国
项目状态:
已结题
起止时间:
1991-04-01 至 2004-03-31
中文摘要
体细胞中的DNA复制是一个不同步的过程。许多
DNA的某些区域复制较早,而其他区域复制较晚。这个
产生这些时间差异的分子机制
复制还没有被很好地理解。最近,使用了一个完全
我们开发的用于研究DNA复制的可溶性系统
我们已经发现,在一个DNA区域启动复制可以激活
一种主动抑制DNA启动的调控途径
在其他可能启动复制的位置进行复制。
具体地说,我们发现在这个复制系统中,
在一个质粒DNA模板上复制会抑制第二个质粒DNA模板的复制
质粒模板。当第一个模板完成复制时,
抑制信号减弱,第二个质粒启动
复制。我们的结果表明,这一信号通路可能
在体细胞周期中,正常调控S的阶段进展。
在这个项目中,旨在识别这一组件的实验
途径进行了描述。具体地说,我们将寻找复制-
CDK2、CDC7、CD45等因子的依赖性抑制
蛋白质,它们是启动DNA复制所必需的。我们会
还要检查是否有一种已被牵连的激酶ATM/R
监管其他依赖DNA的检查点是这一新的
路径。我们还将确定这条途径是否对
S期复制速度与时机的调控
在体细胞中的复制。
我们还一直在调查正在进行的DNA复制是如何抑制
过早地开始有丝分裂。这些研究的结果表明,
有丝分裂酶cdc2的负调控因子weel是稳定的。
虽然DNA复制正在进行,然后在CDC34中迅速降解-
复制完成后的依赖方式。我们的结果
提示通过复制使WEL稳定可以防止启动
有丝分裂在S期。识别本质的实验
引起的成分(cdk2、cds1和F盒受体)
目前的提案对WEL退化进行了描述。
英文摘要
DNA replication in somatic cells is an asynchronous process. Many
regions of DNA replicate early while others replicate late. The
molecular mechanism which generates these differences in timing of
replication are not well understood. Recently, using a completely
soluble system which we have developed for investigating DNA replication
we have found that initiation of replication at one DNA region activates
a regulatory pathway which actively inhibits initiation of DNA
replication at other potential sites of initiation of replication.
Specifically, we find that in this replication system initiation of
replication on one plasmid DNA template inhibits replication of a second
plasmid template. When the first template completes replication, the
inhibitory signal attenuates and the second plasmid initiates
replication. Our results suggest that this signaling pathway may
normally regulate S-phase progression during the somatic cell cycle.
In this project, experiments designed to identify the components of this
pathway are described. Specifically, we will look for a replication-
dependent inhibition of factors such as cdk2 and cdc7 kinase and cdc45
protein, which are essential for initiation of DNA replication. We will
also examine whether a kinase ATM/R which has been implicated in
regulating other DNA-dependent checkpoints is a component of this new
pathway. We will also determine whether this pathway is responsible for
regulating both the rate of replication during S-phase and the timing
of replication in somatic cells.
We have also been investigating how ongoing DNA replication inhibits
premature initiation of mitosis. Results from these studies show that
weel, a negative regulator of the mitotic kinase, cdc2, is stabilized
while DNA replication is ongoing and then rapidly degraded in a cdc34-
dependent manner following completion of replication. Our results
suggest that stabilization of weel by replication prevents initiation
of mitosis during S-phase. Experiments to identify the essential
components (cdk2kinase, cds1 kinase and an F box receptor) which cause
weel degradation are described in the current proposal.
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Identification of a preinitiation step in DNA replication that is independent of origin recognition complex and cdc6, but dependent on cdk2.
鉴定DNA复制中的预启动步骤,该步骤独立于原点识别复合物和CDC6,但取决于CDK2。
DOI:
10.1083/jcb.140.2.271
发表时间:
1998-01-26
期刊:
JOURNAL OF CELL BIOLOGY
影响因子:
7.8
作者:
[Hua, XQH, Newport, J]
通讯作者:
Newport, J
DOI:
10.1083/jcb.137.1.183
发表时间:
1997-04-07
期刊:
The Journal of cell biology
影响因子:
--
作者:
[Hua XH, Yan H, Newport J]
通讯作者:
Newport J
Evidence for a dual role for TC4 protein in regulating nuclear structure and cell cycle progression.
TC4 蛋白在调节核结构和细胞周期进程中发挥双重作用的证据。
DOI:
10.1083/jcb.125.4.705
发表时间:
1994-05
期刊:
The Journal of cell biology
影响因子:
--
作者:
[]
通讯作者:
Xic1 degradation in Xenopus egg extracts is coupled to initiation of DNA replication.
非洲爪蟾卵提取物中 Xic1 的降解与 DNA 复制的启动相关。
DOI:
10.1101/gad.985302
发表时间:
2002
期刊:
Genes & development
影响因子:
10.5
作者:
[You,Zhongsheng, Harvey,Kevin, Kong,Lindsay, Newport,John]
通讯作者:
Newport,John
BIOCHEMICAL PATHWAYS LINKING DNA REPLICATION & MITOSIS
-
批准号:3303887
-
项目类别:
-
资助金额:$14.58万
-
财政年份:1991
-
负责人:john w newport
-
依托单位:
BIOCHEMICAL PATHWAYS LINKING DNA REPLICATION AND MITOSIS
-
批准号:2182651
-
项目类别:
-
资助金额:$18.27万
-
财政年份:1991
-
负责人:john w newport
-
依托单位:
BIOCHEMICAL PATHWAYS LINKING DNA REPLICATION AND MITOSIS
-
批准号:2392130
-
项目类别:
-
资助金额:$18.47万
-
财政年份:1991
-
负责人:john w newport
-
依托单位:
BIOCHEMICAL PATHWAYS LINKING DNA REPLICATION & MITOSIS
-
批准号:3303885
-
项目类别:
-
资助金额:$15.45万
-
财政年份:1991
-
负责人:john w newport
-
依托单位:
BIOCHEMICAL PATHWAYS LINKING DNA REPLICATION & MITOSIS
-
批准号:3303886
-
项目类别:
-
资助金额:$13.8万
-
财政年份:1991
-
负责人:john w newport
-
依托单位:
BIOCHEM PATHWAYS LINKING DNA REPLICATION & MITOSIS
-
批准号:2849091
-
项目类别:
-
资助金额:$22.38万
-
财政年份:1991
-
负责人:john w newport
-
依托单位:
BIOCHEM PATHWAYS LINKING DNA REPLICATION & MITOSIS
-
批准号:6386011
-
项目类别:
-
资助金额:$23.28万
-
财政年份:1991
-
负责人:john w newport
-
依托单位:
BIOCHEM PATHWAYS LINKING DNA REPLICATION & MITOSIS
-
批准号:6179717
-
项目类别:
-
资助金额:$22.92万
-
财政年份:1991
-
负责人:john w newport
-
依托单位:
BIOCHEMICAL PATHWAYS LINKING DNA REPLICATION AND MITOSIS
-
批准号:2182649
-
项目类别:
-
资助金额:$15.31万
-
财政年份:1991
-
负责人:john w newport
-
依托单位:
BIOCHEMICAL PATHWAYS LINKING DNA REPLICATION AND MITOSIS
-
批准号:2182650
-
项目类别:
-
资助金额:$17.03万
-
财政年份:1991
-
负责人:john w newport
-
依托单位:
BIOCHEMICAL PATHWAYS LINKING DNA REPLICATION AND MITOSIS
-
批准号:2684951
-
项目类别:
-
资助金额:$19.12万
-
财政年份:1991
-
负责人:john w newport
-
依托单位:
BIOCHEMICAL ANALYSIS OF NUCLEAR STRUCTURE
-
批准号:2177045
-
项目类别:
-
资助金额:$22.95万
-
财政年份:1984
-
负责人:john w newport
-
依托单位:
BIOCHEMICAL ANALYSIS OF NUCLEAR STRUCTURE
-
批准号:3283356
-
项目类别:
-
资助金额:$18.59万
-
财政年份:1984
-
负责人:john w newport
-
依托单位:
BIOCHEMICAL ANALYSIS OF NUCLEAR STRUCTURE
-
批准号:2177046
-
项目类别:
-
资助金额:$24.4万
-
财政年份:1984
-
负责人:john w newport
-
依托单位:
BIOCHEMICAL ANALYSIS OF NUCLEAR STRUCTURE
-
批准号:2900593
-
项目类别:
-
资助金额:$25.79万
-
财政年份:1984
-
负责人:john w newport
-
依托单位:
BIOCHEMICAL ANALYSIS OF NUCLEAR STRUCTURE
-
批准号:3283360
-
项目类别:
-
资助金额:$21.4万
-
财政年份:1984
-
负责人:john w newport
-
依托单位:
BIOCHEMICAL ANALYSIS OF NUCLEAR STRUCTURE
-
批准号:2177044
-
项目类别:
-
资助金额:$22.16万
-
财政年份:1984
-
负责人:john w newport
-
依托单位:
BIOCHEMICAL ANALYSIS OF NUCLEAR STRUCTURE
-
批准号:3283352
-
项目类别:
-
资助金额:$17.85万
-
财政年份:1984
-
负责人:john w newport
-
依托单位:
BIOCHEMICAL ANALYSIS OF NUCLEAR STRUCTURE
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批准号:6132615
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项目类别:
-
资助金额:$27.29万
-
财政年份:1984
-
负责人:john w newport
-
依托单位:
BIOCHEMICAL ANALYSIS OF NUCLEAR STRUCTURE
-
批准号:2391954
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项目类别:
-
资助金额:$24.4万
-
财政年份:1984
-
负责人:john w newport
-
依托单位:
海外基金