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Normal chromosome ends elicit a limited DNA damage response

ds, and detection of telomeres as damage at this precise time are necessary to trigger the re-formation of a protective telomeric structure," says Karlseder, an assistant professor in the Regulatory Biology Laboratory.

In contrast to damaged strands of DNA, they hypothesize, the repair process never gets fully underway at telomeres. Instead, the very tips of the chromosomes are looped back, tucked in and covered with telomeric proteins.

"The cell tries to fix everything to make sure that the genetic information is safe and complete for the next generation of cells," says Verdun. "But in the case of healthy chromosome tips or telomeres, repair would have disastrous consequences," he adds.

Repairing telomeres would randomly fuse whole chromosomes end-to-end. During the next cell division the sorting mechanism, which ensures that each daughter cell receives a full complement of chromosomes would inevitably rip the fused chromosomes apart.

"Such fusion breakage cycles scramble the genome over time, and cause genome instability, which is a hallmark of cancer cells," explains Karlseder. "This demonstrates the importance of telomeres in preserving genome integrity and preventing cancer development."


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Source:Salk Institute


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