Telomerase subunit Est2 marks internal sites that are prone to accumulate DNA damage
Background:
The main function of telomerase is at the telomeres but under adverse conditions telomerase can bind to internal regions causing deleterious effects as observed in cancer cells.
Results:
By mapping the global occupancy of the catalytic subunit of telomerase (Est2) in the budding yeast Saccharomyces cerevisiae, we reveal that it binds to multiple guanine-rich genomic loci, which we termed “non-telomeric binding sites” (NTBS). We characterize Est2 binding to NTBS. Contrary to telomeres, Est2 binds to NTBS in G1 and G2 phase independently of Est1 and Est3. The absence of Est1 and Est3 renders telomerase inactive at NTBS. However, upon global DNA damage, Est1 and Est3 join Est2 at NTBS and telomere addition can be observed indicating that Est2 occupancy marks NTBS regions as particular risks for genome stability.
Conclusions: Our results provide a novel model of telomerase regulation in the cell cycle using internal regions as “parking spots” of Est2 but marking them as hotspots for telomere addition.
Funding
Spatial regulation of meiotic recombination : WELLCOME TRUST | 200843/Z/16/Z
History
Publication status
- Published
File Version
- Published version
Journal
BMC BiologyISSN
1741-7007Publisher
Springer Science and Business Media LLCPublisher URL
External DOI
Issue
1Volume
19Article number
247Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available
- Yes
Peer reviewed?
- Yes