Normal Chromosome Ends Elicit A Limited DNA Damage Response
Normal Chromosome Ends Elicit A Limited DNA Damage Response: "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 ends, 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.
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.""
'We believe that the localization of repair proteins to chromosome ends, 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.
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.""