The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
RNaseH1 regulates TERRA-telomeric DNA hybrids and telomere maintenance in ALT tumour cells
Open accessAbstract
A fraction of cancer cells maintain telomeres through the telomerase-independent, ‘Alternative Lengthening of Telomeres’ (ALT) pathway. ALT relies on homologous recombination (HR) between telomeric sequences; yet, what makes ALT telomeres recombinogenic remains unclear. Here we show that the RNA endonuclease RNaseH1 regulates the levels of RNA–DNA hybrids between telomeric DNA and the long noncoding RNA TERRA, and is a key mediator of telomere maintenance in ALT cells. RNaseH1 associated to telomeres specifically in ALT cells and its depletion led to telomeric hybrid accumulation, exposure of single-stranded telomeric DNA, activation of replication protein A at telomeres and abrupt telomere excision. Conversely, overexpression of RNaseH1 weakened the recombinogenic nature of ALT telomeres and led to telomere shortening. Altering cellular RNaseH1 levels did not perturb telomere homoeostasis in telomerase-positive cells. RNaseH1 maintains regulated levels of telomeric RNA–DNA hybrids at ALT telomeres to trigger HR without compromising telomere integrity too severely.
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How Shelterin Protects Mammalian Telomeres
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“Recently, accumulating evidence also indicates that ALT cells are characterized by elevated levels of TERRA (refs 6,7,11,12).”
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Telomeric RNA-DNA hybrids affect telomere-length dynamics and senescence
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Bridges, M. C., Daulagala, A. C., & Kourtidis, A. (2021) · Journal of Cell Biology · doi:10.1083/jcb.202009045 · Cited by 1,556
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Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies
Jafri, M. A., Ansari, S. A., Alqahtani, M. H., & Shay, J. W. (2016) · Genome Medicine · doi:10.1186/s13073-016-0324-x · Cited by 716
Heterochromatin: Guardian of the Genome
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Metadata
- Authors
- Arora, R., Lee, Y., Wischnewski, H., Brun, C. M., Schwarz, T., & Azzalin, C. M.
- Venue
- Nature Communications
- Published
- 2014-10-21
- Volume
- 5
- Issue
- 1
- Pages
- 5220-5220
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2021881561
- Cited by
- 469
- References
- 34
- FWCI
- 13.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
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