INITIATION OF DNA REPLICATION BY PHOSPHORYLATION
INITIATION OF DNA REPLICATION BY PHOSPHORYLATION
批准号:
6900958
负责人:
Martine Coue
金额:
$20.72万
依托单位国家:
美国
项目类别:
财政年份:
2001
资助国家:
美国
项目状态:
已结题
起止时间:
2001-07-01 至 2007-06-30
中文摘要
描述(摘自申请人摘要):长期目标
英文摘要
DESCRIPTION (Verbatim from the applicant's abstract): The long-term goal of
this laboratory is to elucidate the mechanism that controls the initiation of
DNA replication in eukaryotes. Two critical steps in this initiation process
are: (1) the assembly of the pre-replication complexes (pre-Rcs) onto the
chromatin; and (2) activation of the pre-Rcs. The ORC, Cdc6 and Mcm proteins
are initiation factors that participate in the formation of the pre-Rcs. This
proposal addresses the role of phosphorylation in the assembly and function of
the pre-Rcs. In particular, phosphorylation of two preRc components, the Cdc6
and the Mcm4 proteins will be closely studied. Using a Xenopus cell-free
system, the cell cycle phosphorylation of the Cdc6 protein will be
characterized and its effect on protein function determined by generating a set
of phosphorylation mutants (Specific Aim 1). The possibility that Cdc6 mediates
the negative role of Cyclin-dependent kinases (Cdks) on pre-Rc assembly will be
tested. In Specific Aim 2, the phosphorylation sites within the Mcm4 protein
will be mapped, the relevant kinase(s) identified and the effect of Mcm4
phosphorylation on the function of the Mcm complex determined. Finally, in
Specific Aim 3 the role of the Cdc7 kinase during the initiation of DNA
replication will be explored. The possibility that Cdc7 is the kinase
responsible for the phosphorylation of the Mcm4 protein while it is bound to
chromatin during S-phase will be tested. Regulation of the pre-Rcs is likely to
be one of the final commitment points for cell proliferation and the physical
target of the controls that ensure alternation of the S- and M-phase and the
controls for the DNA replication checkpoint machinery. Thus, the results of the
proposed experiments will shed light on the process of cell division, as it
occurs normally during development and in healthy animals, and abnormally in
disease processes such as cancer.
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INITIATION OF DNA REPLICATION BY PHOSPHORYLATION
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批准号:6285861
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项目类别:
-
资助金额:$20.72万
-
财政年份:2001
-
负责人:Martine Coue
-
依托单位:
INITIATION OF DNA REPLICATION BY PHOSPHORYLATION
-
批准号:6768575
-
项目类别:
-
资助金额:$20.72万
-
财政年份:2001
-
负责人:Martine Coue
-
依托单位:
INITIATION OF DNA REPLICATION BY PHOSPHORYLATION
-
批准号:6636417
-
项目类别:
-
资助金额:$20.72万
-
财政年份:2001
-
负责人:Martine Coue
-
依托单位:
INITIATION OF DNA REPLICATION BY PHOSPHORYLATION
-
批准号:6520199
-
项目类别:
-
资助金额:$20.72万
-
财政年份:2001
-
负责人:Martine Coue
-
依托单位:
海外基金