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发信人: reer (reer), 信区: Biology
标 题: MCBJC paper for discussion-042803
发信站: The unknown SPACE (Mon Apr 28 19:05:17 2003) WWW-POST
: Cell 2003 Apr 4;113(1):115-25 Related Articles, Links
A Role for Ran-GTP and Crm1 in Blocking Re-Replication.
Yamaguchi R, Newport J.
Department of Biology, University of California, San Diego, 9500 Gilman Drive,
92093, La Jolla, CA, USA
All eukaryotic cells have regulatory mechanisms that limit genomic replication
to a single round each cell cycle. These systems function by blocking
formation of prereplication complexes. The regulatory mechanisms in the yeast
S. cerevisiae have been identified, but these do not appear to be conserved in
metazoans. Using Xenopus egg extracts, we have identified a metazoan-specific
regulatory system that limits replication to a single round. We show that
during S phase, soluble MCM helicase, an essential initiation factor, is
inactivated when it associates with exportin-1/Crm1. Formation of this complex
is dependent on both high Ran-GTP and cdk2 kinase activity. Lowering Ran-GTP
within nuclei or nuclear extracts allows MCM to reassociate with chromatin
during S phase and induces re-replication. Importantly, prevention of
re-replication requires MCM-Crm1 complex formation, but it does not require
export of MCM from the nucleus. Therefore, in metazoans, Crm1 functions in
both nuclear export and blocking of re-replication.
PMID: 12679039 [PubMed - in process]
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When you smile, the whole world lights up.
※ 来源:．The unknown SPACE bbs.mit.edu．[FROM: 129.111.]
发信人: reer (reer), 信区: Biology
标 题: Re: MCBJC paper for discussion-042803
发信站: The unknown SPACE (Mon Apr 28 19:08:30 2003) WWW-POST
Here is a review of this article in the same issue.
If someone does not have the access to the full text, please leave your
email address in my bbs email box. I will send you the full text paper asap.
Cell 2003 Apr 4;113(1):2-4 Related Articles, Links
A new role for ran in ensuring precise duplication of chromosomal DNA.
Blow JJ.
Wellcome Trust Biocentre, University of Dundee, DD1 5EH, Scotland, Dundee,
United Kingdom
To prevent re-replication of DNA, the licensing of replication origins is
inhibited in S phase and G2. New work by Yamaguchi et al. (in this issue of
Cell) shows that the small GTPase Ran can directly inhibit licensing inside
nuclei once CDKs are active late in the cell cycle.
PMID: 12679026 [PubMed - in process]
? ? reer (reer) ??????: ?
: : Cell 2003 Apr 4;113(1):115-25 Related Articles, Links
:
: A Role for Ran-GTP and Crm1 in Blocking Re-Replication.
: Yamaguchi R, Newport J.
: Department of Biology, University of California, San Diego, 9500 Gilman
Drive,
: 92093, La Jolla, CA, USA
: All eukaryotic cells have regulatory mechanisms that limit genomic
replication
: to a single round each cell cycle. These systems function by blocking
: formation of prereplication complexes. The regulatory mechanisms in the
yeast
: S. cerevisiae have been identified, but these do not appear to be conserved
in
: metazoans. Using Xenopus egg extracts, we have identified a
metazoan-specific
: regulatory system that limits replication to a single round. We show that
: during S phase, soluble MCM helicase, an essential initiation factor, is
: inactivated when it associates with exportin-1/Crm1. Formation of this
complex
: is dependent on both high Ran-GTP and cdk2 kinase activity. Lowering Ran-GTP
: within nuclei or nuclear extracts allows MCM to reassociate with chromatin
: during S phase and induces re-replication. Importantly, prevention of
: re-replication requires MCM-Crm1 complex formation, but it does not require
: export of MCM from the nucleus. Therefore, in metazoans, Crm1 functions in
: both nuclear export and blocking of re-replication.
: PMID: 12679039 [PubMed - in process]
:
:
:
:
--
When you smile, the whole world lights up.
※ 来源:．The unknown SPACE bbs.mit.edu．[FROM: 129.111.]
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.]
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