Details

Autor(en) / Beteiligte

• Mei, Yang
• Deng, Zhong
• Vladimirova, Olga
• Gulve, Nitish
• Johnson, F Brad
• Drosopoulos, William C
• Schildkraut, Carl L
• Lieberman, Paul M

Titel

TERRA G-quadruplex RNA interaction with TRF2 GAR domain is required for telomere integrity

Ist Teil von

• Scientific reports, 2021-02, Vol.11 (1), p.3509-3509, Article 3509

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2021

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.