Exploring TRF2-dependent DNA distortion through single-DNA manipulation studies

DOI: 10.1038/s42003-024-05838-x

Authors: Xiaodan Zhao (National University of Singapore) , Vinod Kumar Vogirala (Nanyang Technology University; Diamond Light Source) , Meihan Liu (National University of Singapore) , Yu Zhou (National University of Singapore) , Daniela Rhodes (National University of Singapore; Medical Research Council) , Sara Sandin (Nanyang Technology University; Umeå University) , Jie Yan (National University of Singapore; Tianjin University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Communications Biology , VOL 7

State: Published (Approved)
Published: February 2024

Abstract: TRF2 is a component of shelterin, a telomere-specific protein complex that protects the ends of mammalian chromosomes from DNA damage signaling and improper repair. TRF2 functions as a homodimer and its interaction with telomeric DNA has been studied, but its full-length DNA-binding properties are unknown. This study examines TRF2’s interaction with single-DNA strands and focuses on the conformation of the TRF2-DNA complex and TRF2’s preference for DNA chirality. The results show that TRF2-DNA can switch between extended and compact conformations, indicating multiple DNA-binding modes, and TRF2’s binding does not have a strong preference for DNA supercoiling chirality when DNA is under low tension. Instead, TRF2 induces DNA bending under tension. Furthermore, both the N-terminal domain of TRF2 and the Myb domain enhance its affinity for the telomere sequence, highlighting the crucial role of multivalent DNA binding in enhancing its affinity and specificity for telomere sequence. These discoveries offer unique insights into TRF2’s interaction with telomeric DNA.

Subject Areas: Biology and Bio-materials, Chemistry


Technical Areas:

Added On: 05/02/2024 08:16

Documents:
s42003-024-05838-x.pdf

Discipline Tags:

Biochemistry Chemistry Structural biology Biophysics Life Sciences & Biotech

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