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Once is enough when it comes to DNA replication—for every cell cycle, chromosomes are replicated just one time to prevent genomic instability. On page 473, Melixetian et al. identify a protein that polices this limitation in human cells.$ o" H5 p# s) L
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The replication police officer is Geminin, which prevents replication origins in Xenopus from recruiting licensing proteins that can give the replication go-ahead. In frogs, Geminin does not work alone, as its loss does not induce rereplication. But in human cells, the authors find, Geminin runs the show.
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RNAi of Geminin led to additional rounds of replication in both normal and cancerous human cell lines. Rereplication required licensing proteins, suggesting that Geminin works in mammalian cells as it does in frogs.
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Y1 s: Z0 C8 g4 r6 ^+ [Rereplicating cells accumulated foci of proteins that bind to double-stranded DNA breaks. The foci might be a result of colliding replication forks that are recognized as breaks. Whatever their genesis, they resulted in activation of the DNA damage checkpoint controlled by the CHK1 kinase, thus preventing entry into mitosis., r+ D0 i9 e g! S; y& W& K% i
0 ]9 b j# X; o0 |% j. U* n+ ]If the checkpoint was then turned off, the cells entered mitosis but died before division was complete. If cells lacking Geminin could somehow escape the checkpoint and yet survive (through other unknown mutations), they would be a cancerous nightmare, complete with genomic instability and uncontrolled proliferation.(Loss of Geminin leads to multiple copies) |
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发表于 2009-3-6 08:19
发表于 2015-6-13 15:35
