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The telomerase reverse transcriptase elongates reversed replication forks at telomeric repeats

Huda, Armela,
; 
Arakawa, Hiroshi
; 
Mazzucco, Giulia
; 
Galli, Martina
; 
Petrocelli, Valentina
; 
Casola, Stefano
; ; 
Dokasani, Ylli
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Journal article
Date
2023-03-22
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Lu Chen Lab (Temple University)
Fox Chase Cancer Center
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Cancer and Cellular Biology
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http://hdl.handle.net/20.500.12613/9091
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ChenEtAl-JournalArticle-2023-03.pdf
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DOI
https://doi.org/10.1126/sciadv.adf2011
Abstract
The telomerase reverse transcriptase elongates telomeres to prevent replicative senescence. This process requires exposure of the 3′-end, which is thought to occur when two sister telomeres are generated at replication completion. Using two-dimensional agarose gel electrophoresis (2D-gels) and electron microscopy, we found that telomeric repeats are hotspots for replication fork reversal. Fork reversal generates 3′ telomeric ends before replication completion. To verify whether these ends are elongated by telomerase, we probed de novo telomeric synthesis in situ and at replication intermediates by reconstituting mutant telomerase that adds a variant telomere sequence. We found variant telomeric repeats overlapping with telomeric reversed forks in 2D-gels, but not with normal forks, nontelomeric reversed forks, or telomeric reversed forks with a C-rich 3′-end. Our results define reversed telomeric forks as a substrate of telomerase during replication.
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Citation
Huda A, Arakawa H, Mazzucco G, Galli M, Petrocelli V, Casola S, et al. The telomerase reverse transcriptase elongates reversed replication forks at telomeric repeats. Sci. Adv. 2023 Mar 22;9. doi:10.1126/sciadv.adf2011.
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American Association for the Advancement of Science
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Science Advances, Vol. 9, Iss. 12
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