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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