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Scc2/Nipbl hops between chromosomal cohesin rings after loading

James D.P. Rhodes, Davide Mazza, Kim A. Nasmyth, Stephan Uphoff
doi: https://doi.org/10.1101/136754
James D.P. Rhodes
1Department of Biochemistry, Oxford University, South Parks Rd, Oxford, OX1 3QU, UK
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Davide Mazza
2Istituto Scientifico Ospedale San Raffaele, Centro di Imaging Sperimentale, 20132, Milano, Italy
3Fondazione CEN, European Center for Nanomedicine, 20133, Milano, Italy
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Kim A. Nasmyth
1Department of Biochemistry, Oxford University, South Parks Rd, Oxford, OX1 3QU, UK
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Stephan Uphoff
1Department of Biochemistry, Oxford University, South Parks Rd, Oxford, OX1 3QU, UK
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Abstract

The cohesin complex mediates DNA-DNA interactions both between (sister chromatid cohesion) and within chromosomes (DNA looping) via a process thought to involve entrapment of DNAs within its tripartite ring. It has been suggested that intra- chromosome loops are generated through processive extrusion of DNAs through the lumen of cohesin’s ring. Scc2 (Nipbl) is essential for loading cohesin onto chromosomes but not for maintaining sister chromatid cohesion following DNA replication. It has therefore been assumed that Scc2 is involved exclusively in the cohesin loading process. However, it is possible that the stimulation of cohesin’s ABC-like ATPase by Scc2 also has a post-loading function, for example driving loop extrusion. Using fluorescence recovery after photobleaching (FRAP) and single-molecule tracking, we show that Scc2 binds dynamically to chromatin, principally through an association with cohesin. Scc2’s movement within chromatin is consistent with a “stop-and-go” or “hopping” motion. We suggest that a low diffusion coefficient, a low stoichiometry relative to cohesin, and a high affinity for chromosomal cohesin enables Scc2 to move rapidly from one chromosomal cohesin complex to another, performing a function distinct from loading.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted May 11, 2017.
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Scc2/Nipbl hops between chromosomal cohesin rings after loading
James D.P. Rhodes, Davide Mazza, Kim A. Nasmyth, Stephan Uphoff
bioRxiv 136754; doi: https://doi.org/10.1101/136754
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Scc2/Nipbl hops between chromosomal cohesin rings after loading
James D.P. Rhodes, Davide Mazza, Kim A. Nasmyth, Stephan Uphoff
bioRxiv 136754; doi: https://doi.org/10.1101/136754

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