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A sloppy checkpoint

If the G2 checkpoint were a building inspector, it would get fired for negligence. Deckbar et al. show on page 749 that the checkpoint, which is supposed to halt division after chromosome damage, allows cells to proceed into mitosis even if they harbor fractured DNA.

The G2 checkpoint interrupts the cell cycle to allow repair of double-stranded DNA breaks (DSBs). But the checkpoint isn't perfect, as the researchers found when they irradiated normal human fibroblasts and Artemis cells, which have a normal checkpoint but sluggish DSB repair. Each of the cells that went on into mitosis had one to two chromosome breaks, which is 10 times the background value.

Not every DSB shows up as a complete chromosome break. So to gauge the number of DSBs that are slipping past the checkpoint, the researchers counted the number of repair foci, where enzymes have begun—but not finished—mending DNA. Fibroblasts left G2 with 20 foci. Other methods gave similar values for unfixed DSBs, indicating that the checkpoint has a threshhold of 10 to 20 breaks.

Only one DSB is needed to activate this checkpoint in yeast, according to previous studies. Mammalian cells might be sloppier because they carry much more DNA. Whether unrepaired breaks cause trouble is unclear. Many of them might get fixed at the subsequent G1 checkpoint.

Mitch Leslie

mitchleslie{at}comcast.net

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This Article Full Text (PDF, 768K) 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 Leslie, M. Search for Related Content PubMed Articles by Leslie, M. Social Bookmarking                            What's this?