1. Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK
2. Computational Genome Analysis Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK
3. Riken Genomic Science Center, Human Genome Research Group, Genome Informatics Team, 1-7-22-W417 Suehiro, Tsurumi, Yokohama City, Kanagawa, 230-0045, Japan
4. Center for Biological Resources and Informatics, Division of Gene Research, and Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama, 226-8501, Japan
5. Science of Biological Supramolecular Systems, Graduate School of Integrated Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan
6. Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi 1-1-1, Tokyo 113-0032, Japan
7. Research Center for Advanced Science and Technology, Mitsubishi Research Institute Inc., 2-3-6 Ohtemachi, Chiyoda-ku, Tokyo, 100-8141, Japan
8. SORST, Japan Science and Technology Agency, Yayoi 1-1-1, Tokyo 113-0032, Japan
9. These authors contributed equally to this work

Correspondence to: Frank Uhlmann^1,9 Email: frank.uhlmann@cancer.org.uk

Abstract

Sister chromatids, the products of eukaryotic DNA replication, are held together by the chromosomal cohesin complex after their synthesis. This allows the spindle in mitosis to recognize pairs of replication products for segregation into opposite directions^{1, 2, 3, 4, 5, 6}. Cohesin forms large protein rings that may bind DNA strands by encircling them⁷, but the characterization of cohesin binding to chromosomes in vivo has remained vague. We have performed high resolution analysis of cohesin association along budding yeast chromosomes III–VI. Cohesin localizes almost exclusively between genes that are transcribed in converging directions. We find that active transcription positions cohesin at these sites, not the underlying DNA sequence. Cohesin is initially loaded onto chromosomes at separate places, marked by the Scc2/Scc4 cohesin loading complex⁸, from where it appears to slide to its more permanent locations. But even after sister chromatid cohesion is established, changes in transcription lead to repositioning of cohesin. Thus the sites of cohesin binding and therefore probably sister chromatid cohesion, a key architectural feature of mitotic chromosomes, display surprising flexibility. Cohesin localization to places of convergent transcription is conserved in fission yeast, suggesting that it is a common feature of eukaryotic chromosomes.

1. Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK
2. Computational Genome Analysis Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK
3. Riken Genomic Science Center, Human Genome Research Group, Genome Informatics Team, 1-7-22-W417 Suehiro, Tsurumi, Yokohama City, Kanagawa, 230-0045, Japan
4. Center for Biological Resources and Informatics, Division of Gene Research, and Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama, 226-8501, Japan
5. Science of Biological Supramolecular Systems, Graduate School of Integrated Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan
6. Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi 1-1-1, Tokyo 113-0032, Japan
7. Research Center for Advanced Science and Technology, Mitsubishi Research Institute Inc., 2-3-6 Ohtemachi, Chiyoda-ku, Tokyo, 100-8141, Japan
8. SORST, Japan Science and Technology Agency, Yayoi 1-1-1, Tokyo 113-0032, Japan
9. These authors contributed equally to this work

Correspondence to: Frank Uhlmann^1,9 Email: frank.uhlmann@cancer.org.uk

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