Principal Investigator, IFOM ETS – The AIRC Institute of Molecular Oncology, Milan, Italy

Two things that can go wrong at telomeric repeats

Host: G. Del Sal

Each end of our linear chromosomes is capped by tandem TTAGGG repeats that extend

for 10-12 kb at birth, but are gradually lost as we age. This loss of telomeric repeats can

promote both cellular senescence and genome instability, two hallmarks of aging and

tumorigenesis. We study the consequences of DNA damage and replication stress on the

maintenance of telomeres. To this end we have developed procedures to purify mammalian

telomeres and visualize their structure in electron microscopy. By visualizing damaged

telomeres, we have identified DNA structures associated with erosion of telomeric repeats

and formation of extrachromosomal circular DNA. By visualizing replicating telomeres,

we observed an increased probability of replication fork reversal at these sequences.

Interestingly, the reversed telomeric forks become a substrate for telomerase; the reverse

transcriptase, which can add de novo telomeric repeats to chromosome ends. Elongation

of reversed forks by telomerase, could have important implication for genome instability

and tumorigenesis.


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