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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