MassIVE MSV000085772

Complete Public PXD020419

Mammalian telomeres reforged with non-telomeric sequences

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Description

Telomere is a highly refined system for maintaining the stability of linear chromosomes. Most telomeres rely on simple repetitive sequences and telomerase enzymes, but in some species or telomerase-defective situations, alternative telomere lengthening (ALT) mechanism is utilized to protect chromosomal ends. Telomere loss can induce telomere recombination by which specific sequences can be recruited into telomeres. However, canonical telomeric repeat-based telomeres have been found in mammals. Here, we show that mammalian telomeres can also be completely reconstituted using a non-telomeric unique sequence. We found that a specific subtelomeric element, named as mouse template for ALT (mTALT), is utilized for repairing telomeric DNA damage and composing new telomeric sequences in mouse embryonic stem cells. We found a high-level of non-coding mTALT transcript despite the heterochromatic nature of mTALT-based telomere. After ALT activation, the increased HMGN1, a non-histone chromosomal protein, contributed to maintaining telomere stability by regulating telomeric transcriptions. Our findings reveal novel molecular features of potential telomeric sequences which can reconstitute telomeres during cancer formation and evolution. [doi:10.25345/C5MN11] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: telomere ; alternative lengthening of telomeres ; copy number variation ; telomere damage ; HMGN1 ; telomere repeat-containing RNA

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Principal Investigators:
(in alphabetical order) 		Junho Lee, Seoul National University, Korea
Submitting User: sunnyshin54
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