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Geminin halts DNA synthesis

Loss of Geminin leads to multiple copies of the ß-globin gene (red).

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.

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.

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.

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.

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.

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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Loss of Geminin induces rereplication in the presence of functional p53

Marina Melixetian, Andrea Ballabeni, Laura Masiero, Patrizia Gasparini, Raffaella Zamponi, Jiri Bartek, Jiri Lukas, and Kristian Helin
J. Cell Biol. 2004 165: 473-482. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 2974K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Related Collections Related Article Social Bookmarking                            What's this?