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Article Abstract
Telomere dysfunction causes chromosomal instability which is associated with many cancers and age-related diseases. The non-coding telomeric repeat-containing RNA (TERRA) forms a structural and regulatory component of the telomere that is implicated in telomere maintenance and chromosomal end protection. The basic N-terminal Gly/Arg-rich (GAR) domain of telomeric repeat-binding factor 2 (TRF2) can bind TERRA but the structural basis and significance of this interaction remains poorly understood. Here, we show that TRF2 GAR recognizes G-quadruplex features of TERRA. We show that small molecules that disrupt the TERRA-TRF2 GAR complex, such as N-methyl mesoporphyrin IX (NMM) or genetic deletion of TRF2 GAR domain, result in the loss of TERRA, and the induction of γH2AX-associated telomeric DNA damage associated with decreased telomere length, and increased telomere aberrations, including telomere fragility. Taken together, our data indicates that the G-quadruplex structure of TERRA is an important recognition element for TRF2 GAR domain and this interaction between TRF2 GAR and TERRA is essential to maintain telomere stability.
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| http://dx.doi.org/10.1038/s41598-021-82406-x | DOI Listing |
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TERRA G-quadruplex RNA interaction with TRF2 GAR domain is required for telomere integrity.
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Telomere dysfunction causes chromosomal instability which is associated with many cancers and age-related diseases. The non-coding telomeric repeat-containing RNA (TERRA) forms a structural and regulatory component of the telomere that is implicated in telomere maintenance and chromosomal end protection. The basic N-terminal Gly/Arg-rich (GAR) domain of telomeric repeat-binding factor 2 (TRF2) can bind TERRA but the structural basis and significance of this interaction remains poorly understood.
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Article Synopsis
- The telomerase complex, composed of proteins and nucleic acids, is essential for maintaining and repairing telomeres, while the Telosome is a network of proteins that supports this function.
- Dyskeratosis congenita (DC) is a rare genetic disorder linked to mutations in telomerase and Telosome components, presenting symptoms similar to premature aging and highlighting the importance of telomerase in cellular health.
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Role of 53BP1 oligomerization in regulating double-strand break repair.
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