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Normal chromosome ends elicit a limited DNA damage response

Researchers at the Salk Institute for Biological Studies discovered that cells co-opted the machinery that usually repairs broken strands of DNA to protect the integrity of chromosomes. This finding solves for the first time an important question that has long puzzled scientists.

The natural ends of chromosomes look just like broken strands of DNA that a cell's repair machinery is designed to fix. But mending chromosome ends, or telomeres, would set the stage for the development of cancer in successive generation of cells.

To prevent the cell's DNA repair machinery from confusing telomeres with broken strands of DNA that need to be repaired, the tips of chromosomes are tucked in and shielded by a phalanx of proteins, forming a protective "cap".

Ironically, to form this protective structure at the end of chromosomes, nature solicited help from the very same repair machinery whose misguided repair attempts the cap is supposed to hold at bay, reports the Salk team, led by Jan Karlseder, in the current issue of Molecular Cell.

Scientists had long surmised that the protective telomere-protein complex had to unravel when enzymes need to gain access in order to copy the chromosome's DNA in preparation for cell division. And if so, they wondered, why didn't the presumably exposed chromosome ends trigger a DNA damage response?

Turns out they do, at least to a limited extend.

"During a small window right after DNA replication, when the cell gets ready for cell division, chromosome ends are exposed," says research fellow and first author Ramiro Verdun who emphasizes that, "it would be very unhealthy for the cell if it happened at any other time."

In addition, Verdun and his colleagues found that several well-known members of the DNA damage response machinery ?recruited by the now unprotected telomeres - congregate at the tips of chromosomes.

"We believe that the localization of repair proteins to chromosome en
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Source:Salk Institute


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