Functional interplay between SA1 and TRF1 in telomeric DNA binding and DNA-DNA pairing.
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.
School of Bioscience and Engineering, South China University of Technology, Guangzhou, Guangdong 510006, P.R. China Physics Department, North Carolina State University, Raleigh, North Carolina, NC 27695, USA.
Jiangguo
J
Lin
Physics Department, North Carolina State University, Raleigh, North Carolina, NC 27695, USA.
Preston
P
Countryman
Department of BioSciences, Rice University, Houston, TX 77005, USA Institute of Microbiology and College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China.
Haijiang
H
Chen
Physics Department, North Carolina State University, Raleigh, North Carolina, NC 27695, USA.
Hai
H
Pan
Department of BioSciences, Rice University, Houston, TX 77005, USA.
Yanlin
Y
Fan
Department of BioSciences, Rice University, Houston, TX 77005, USA.
Yunyun
Y
Jiang
Physics Department, North Carolina State University, Raleigh, North Carolina, NC 27695, USA.
Parminder
P
Kaur
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China.
Wang
W
Miao
Biomanufacturing Training and Education Center, North Carolina State University, Raleigh, North Carolina, NC 27695, USA.
Gisele
G
Gurgel
Division of Biophysics, Universität Osnabrück, Barbarstrasse 11, 49076 Osnabrück, Germany.
Changjiang
C
You
Division of Biophysics, Universität Osnabrück, Barbarstrasse 11, 49076 Osnabrück, Germany.
Jacob
J
Piehler
School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK.
Neil M
NM
Kad
Physics Department, North Carolina State University, Raleigh, North Carolina, NC 27695, USA.
Robert
R
Riehn
Department of Environmental and Occupational Health, University of Pittsburgh, PA 15213, USA.
Patricia L
PL
Opresko
Kimmel Center for Biology and Medicine at the Skirball Institute, Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
Susan
S
Smith
Department of BioSciences, Rice University, Houston, TX 77005, USA.
Yizhi Jane
YJ
Tao
Physics Department, North Carolina State University, Raleigh, North Carolina, NC 27695, USA hong_wang@ncsu.edu.
Hong
H
Wang
D024761:AT-Hook Motifs / Q000235:genetics; D002842:Chromatids / Q000235:genetics / Q000648:ultrastructure; D020090:Chromosome Segregation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D006801:Humans; D018625:Microscopy, Atomic Force; D008938:Mitosis / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D016615:Telomere / Q000235:genetics* / Q000648:ultrastructure; D034501:Telomere-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D035321:Telomeric Repeat Binding Protein 1 / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C108522:STAG1 protein, human; C440868:TINF2 protein, human; D034501:Telomere-Binding Proteins; D035321:Telomeric Repeat Binding Protein 1