Functional interplay between SA1 and TRF1 in telomeric DNA binding and DNA–DNA pairing

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Lin, Jiangguo ; Countryman, Preston ; Chen, Haijiang ; Pan, Hai ; Fan, Yanlin ; Jiang, Yunyun ; Kaur, Parminder ; Miao, Wang ; Gurgel, Gisele ; You, Changjiang ; Piehler, Jacob ; Kad, Neil M. ; Riehn, Robert ; Opresko, Patricia L. ; Smith, Susan ; Tao, Yizhi Jane ; Wang, Hong (2016)
  • Publisher: Oxford University Press
  • Journal: Nucleic Acids Research, volume 44, issue 13, pages 6,363-6,376 (issn: 0305-1048, eissn: 1362-4962)
  • Related identifiers: doi: 10.1093/nar/gkw518, pmc: PMC5291270
  • Subject: Q | Nucleic Acid Enzymes

Proper chromosome alignment and segregation during mitosis depend on cohesion between sister chromatids. Cohesion is thought to occur through the entrapment of DNA within the tripartite ring (Smc1, Smc3 and Rad21) with enforcement from a fourth subunit (SA1/SA2). Surprisingly, cohesin rings do not play a major role in sister telomere cohesion. Instead, this role is replaced by SA1 and telomere binding proteins (TRF1 and TIN2). Neither the DNA binding property of SA1 nor this unique telomere cohesion mechanism is understood. Here, using single-molecule fluorescence imaging, we discover that SA1 displays two-state binding on DNA: searching by one-dimensional (1D) free diffusion versus recognition through subdiffusive sliding at telomeric regions. The AT-hook motif in SA1 plays dual roles in modulating non-specific DNA binding and subdiffusive dynamics over telomeric regions. TRF1 tethers SA1 within telomeric regions that SA1 transiently interacts with. SA1 and TRF1 together form longer DNA-DNA pairing tracts than with TRF1 alone, as revealed by atomic force microscopy imaging. These results suggest that at telomeres cohesion relies on the molecular interplay between TRF1 and SA1 to promote DNA-DNA pairing, while along chromosomal arms the core cohesin assembly might also depend on SA1 1D diffusion on DNA and sequence-specific DNA binding.
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