Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.09.12.286559v1?rss=1

Authors: Pan, H., Kaur, P., Liu, M., Xu, P., Mahn, C., Barnes, R., Tang, Q., Hao, P., Bhattaram, D., You, C., Piehler, J., Weninger, K., Riehn, R., Smith, S., Opersko, P. L., Wang, H.

Abstract:

The shelterin complex consisting of TRF1, TRF2, RAP1, TIN2, TPP1, and POT1, functions to prevent false recognition of telomeres as double-strand DNA breaks, and to regulate telomerase and DNA repair protein access. TIN2 is a core component linking double-stranded telomeric DNA binding proteins (TRF1 and TRF2) and proteins at the 3' overhang (TPP1-POT1). Since TIN2 does not bind to DNA, determining its mechanistic function has been elusive. Here, we investigated DNA molecular structures promoted by TRF1-TIN2 using complementary single-molecule imaging platforms. We demonstrate that TIN2S and TIN2L isoforms facilitate TRF1-mediated DNA compaction (cis-interactions) and DNA-DNA bridging (trans-interactions) in a telomeric sequence-dependent manner. Pre-incubation of TRF1 with its regulator protein Tankyrase 1 significantly reduces TRF1-TIN2 mediated DNA-DNA bridging, whereas TIN2 protects the disassembly of TRF1-TIN2 DNA bridges upon Tankyrase 1 addition. Our study provides evidence that TIN2 functions to promote TRF1 mediated trans-interactions of telomeric DNA, and provides new insight into sister telomere cohesion.

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