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The authors created extra telomeres in yeast by inducing DSBs next to an internally inserted telomeric repeat. Unlike other DSBs, telomere-adjacent breaks induced only short-lived checkpoint delays. This temporary checkpoint delay probably occurs while telomeric proteins assemble at the new DNA ends—a process that only gets started once telomeric sequences are close to a DNA end. In normal cells, the telomeric proteins are already assembled, so checkpoints never get started.
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One simple mechanistic explanation calls for a telomere-bound inhibitor that blocks the activity of Mec1, which initiates the checkpoint response from DSBs. Kinase activity of a mammalian Mec1 homologue, in fact, is known to be inhibited by overexpression of the TRF2 telomeric protein.
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( _4 {7 x. B; y' o4 z* t, j; C1 t- QAnticheckpoints worked on DSBs as far as 600 bp from the telomeric repeats. Thus, says Weinert, "any problems in the DNA near the telomere may not benefit from checkpoint regulation." This might explain why the DNA internal to telomeres is usually repetitive. "With repeats," says Weinert, "breaks can be repaired off nearby intact sequences as a way to compensate for having no checkpoint."(The ends of eukaryotic chromosomes look ) |
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发表于 2009-3-6 08:56
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