Journal
SCIENCE
Volume 290, Issue 5500, Pages 2309-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.290.5500.2309
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Funding
- NCI NIH HHS [CA60499] Funding Source: Medline
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In all eukaryotic organisms, inappropriate firing of replication origins during the G(2) phase of the cell cycle is suppressed by cyclin-dependent kinases. Multicellular eukaryotes contain a second putative inhibitor of re-replication called geminin, Geminin is believed to block binding of the mini-chromosome maintenance (MCM) complex to origins of replication, but the mechanism of this inhibition is unclear. Here we show that geminin interacts tightly with Cdt1, a recently identified replication initiation factor necessary for MCM Loading. The inhibition of DNA replication by geminin that is observed in cell-free DNA replication extracts is reversed by the addition of excess Cdt1. In the normal cell cycle, Cdt1 is present only in G(1) and S, whereas geminin is present in S and G(2) phases of the cell cycle. Together, these results suggest that geminin inhibits inappropriate origin firing by targeting Cdt1.
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