发信人: Marble (小石头哥哥), 信区: Biology
标 题: Re: MCBJC paper for discussion-042803
发信站: The unknown SPACE (Thu May 1 20:25:20 2003), 站内信件

this is a good paper that tries to dissect the regulatory
mechanism of strict control on DNA replication during cell
cycle. to ensure only one round of DNA replication at each
S phase, yeast S. cerevisiae exploits cdk2 kinase to regulate
functionally reduntant pathways: degradation of Cdc6, export
of MCM from the nucleus, and phosphorylation of ORC. however,
the mechanism in metazoan is unclear while the cellular
targets of cdk2 have not been completely understood yet.
the author (only one besides the senior author) used Xenopus
egg extract to set up the system to study DNA replication.
it has been shown that nuclear import (Ran and importins)
is important to nonimport processes, and the author started
by addressing Ran in MCM loading onto origin during DNA
replication. i am not sure about their logic here since i
do not know whether Ran has been implicated in this process
before. the basic methodology of this paper is to address
the MCM loading biochemically; and different Ran mutant
proteins were used for such purpose. after establishing the
role of Ran in MCM loading, the function of cdk2 was addressed.
i am a little bit surprised that inhibitor of cdk2 rather
than mutant cdk2 was used. it is still important to address
the phosphorylation targets of cdk2, and whether MCM serves
as the phosphorylation substrate, what would happen when the
phosphorylate sites are abolished. besides, i think there
are other cellular pathways that ensure the restricted DNA
replication than Ran-GTP.



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※ 来源:．The unknown SPACE bbs.mit.edu．[FROM: 128.118.]