Conserved and unique features of terminal telomeric sequences in ALT-positive cancer cells
A significant portion of human cancers utilize a recombination-based pathway, alternative lengthening of telomeres (ALT), to maintain telomere length. Targeting the ALT is of growing interest as a cancer therapy, yet a substantial knowledge gap remains regarding the basic features of telomeres in AL...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2025-08-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/106657 |
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| author | Benura Azeroglu Wei Wu Raphael Pavani Ranjodh Singh Sandhu Tadahiko Matsumoto André Nussenzweig Eros Lazzerini-Denchi |
| author_facet | Benura Azeroglu Wei Wu Raphael Pavani Ranjodh Singh Sandhu Tadahiko Matsumoto André Nussenzweig Eros Lazzerini-Denchi |
| author_sort | Benura Azeroglu |
| collection | DOAJ |
| description | A significant portion of human cancers utilize a recombination-based pathway, alternative lengthening of telomeres (ALT), to maintain telomere length. Targeting the ALT is of growing interest as a cancer therapy, yet a substantial knowledge gap remains regarding the basic features of telomeres in ALT-positive cells. To address this, we adopted END-seq, an unbiased sequencing-based approach, to define the identity and regulation of the terminal sequences of chromosomes in ALT cells. Our data reveal that the terminal portions of chromosomes in ALT cells contain canonical telomeric sequences with the same terminus bias (-ATC) observed in non-ALT cells. Furthermore, as reported for non-ALT cells, POT1 is required to preserve the precise regulation of the 5′ end in cells that maintain telomere length using the ALT pathway. Thus, the regulation of the terminal 5′ of chromosomes occurs independently of the mechanism of telomere elongation. Additionally, we employed an S1 endonuclease-based sequencing method to determine the presence and origin of single-stranded regions within ALT telomeres. These data shed light on conserved and unique features of ALT telomeres. |
| format | Article |
| id | doaj-art-1d4147e2fbf84be38027cb00c9ce17d6 |
| institution | DOAJ |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-1d4147e2fbf84be38027cb00c9ce17d62025-08-20T03:16:25ZengeLife Sciences Publications LtdeLife2050-084X2025-08-011410.7554/eLife.106657Conserved and unique features of terminal telomeric sequences in ALT-positive cancer cellsBenura Azeroglu0https://orcid.org/0000-0001-7243-384XWei Wu1Raphael Pavani2https://orcid.org/0000-0002-7187-2995Ranjodh Singh Sandhu3https://orcid.org/0009-0008-2340-3423Tadahiko Matsumoto4André Nussenzweig5Eros Lazzerini-Denchi6https://orcid.org/0000-0001-5378-4644Laboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, United StatesLaboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, United StatesLaboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, United StatesLaboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, United StatesLaboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, United StatesLaboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, United StatesLaboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, United StatesA significant portion of human cancers utilize a recombination-based pathway, alternative lengthening of telomeres (ALT), to maintain telomere length. Targeting the ALT is of growing interest as a cancer therapy, yet a substantial knowledge gap remains regarding the basic features of telomeres in ALT-positive cells. To address this, we adopted END-seq, an unbiased sequencing-based approach, to define the identity and regulation of the terminal sequences of chromosomes in ALT cells. Our data reveal that the terminal portions of chromosomes in ALT cells contain canonical telomeric sequences with the same terminus bias (-ATC) observed in non-ALT cells. Furthermore, as reported for non-ALT cells, POT1 is required to preserve the precise regulation of the 5′ end in cells that maintain telomere length using the ALT pathway. Thus, the regulation of the terminal 5′ of chromosomes occurs independently of the mechanism of telomere elongation. Additionally, we employed an S1 endonuclease-based sequencing method to determine the presence and origin of single-stranded regions within ALT telomeres. These data shed light on conserved and unique features of ALT telomeres.https://elifesciences.org/articles/106657ALTtelomeresssDNAEND-seq |
| spellingShingle | Benura Azeroglu Wei Wu Raphael Pavani Ranjodh Singh Sandhu Tadahiko Matsumoto André Nussenzweig Eros Lazzerini-Denchi Conserved and unique features of terminal telomeric sequences in ALT-positive cancer cells eLife ALT telomeres ssDNA END-seq |
| title | Conserved and unique features of terminal telomeric sequences in ALT-positive cancer cells |
| title_full | Conserved and unique features of terminal telomeric sequences in ALT-positive cancer cells |
| title_fullStr | Conserved and unique features of terminal telomeric sequences in ALT-positive cancer cells |
| title_full_unstemmed | Conserved and unique features of terminal telomeric sequences in ALT-positive cancer cells |
| title_short | Conserved and unique features of terminal telomeric sequences in ALT-positive cancer cells |
| title_sort | conserved and unique features of terminal telomeric sequences in alt positive cancer cells |
| topic | ALT telomeres ssDNA END-seq |
| url | https://elifesciences.org/articles/106657 |
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