{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T01:14:45Z","timestamp":1788484485182,"version":"build-2803163510"},"posted":{"date-parts":[[2026,8,6]]},"group-title":"Genetics","reference-count":80,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"name":"National Institute of Health","award":["1R35 GM-118189-06"],"award-info":[{"award-number":["1R35 GM-118189-06"]}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"crossref","award":["HG003143"],"award-info":[{"award-number":["HG003143"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,1]]},"abstract":"<jats:p>The protein complex cohesin plays critical roles in genomic stability by tethering together sister chromatids at their pericentric regions and along their arms from S phase until anaphase. Cohesin-mediated pericentric cohesion prevents aneuploidy by ensuring bipolar attachment of sister kinetochores. Arm cohesion prevents loss of heterozygosity by biasing DNA repair via recombination between sister chromatids rather than between homologs. Here, we investigate in yeast whether cohesin also enhances genomic stability by suppressing unequal sister chromatid exchange (USCE) between repetitive sequences. In wild-type cells, the USCE rate between repeats 4kb apart (proximal) was 15X higher than repeats 68kb apart (distal). The USCE between distal repeats but not proximal repeats increased 4 to 7-fold in mutants with altered cohesin subunits or auxiliary factors. The level of increased distal USCE corresponded with reduced arm cohesion, reduced density of cohesion arm sites, and higher sister loci mobility. Our results suggest that high density of arm cohesion sites confines repair of DNA damage to local sequences. When the density of cohesion sites decreases, sister chromatid sequences are less confined, thereby enhancing distal repeat interactions and USCE. Another set of mutations disrupted both DNA replication and cohesin loading at the replication fork during S phase. Remarkably, distal USCE in these mutants increased approximately 100-fold and was 6-fold more likely than proximal USCE. This preferential hyperdistal USCE can be explained by an aberrant sister-chromatid structure that is normally prevented by proper coupling of cohesin function and replication.<\/jats:p>","DOI":"10.64898\/2026.07.31.742155","type":"posted-content","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T15:35:16Z","timestamp":1786030516000},"source":"Crossref","is-referenced-by-count":0,"title":["Cohesin promotes genomic stability by suppressing unequal sister chromatid exchange"],"prefix":"10.64898","author":[{"given":"Vincent","family":"Guacci","sequence":"first","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Minchell","sequence":"additional","affiliation":[{"name":"Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA"},{"name":"Howard Hughes Medical Institute, Chevy Chase, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tik","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Venev","sequence":"additional","affiliation":[{"name":"Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA"},{"name":"Howard Hughes Medical Institute, Chevy Chase, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Job","family":"Dekker","sequence":"additional","affiliation":[{"name":"Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA"},{"name":"Howard Hughes Medical Institute, Chevy Chase, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3742-6294","authenticated-orcid":false,"given":"Douglas","family":"Koshland","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026090318103219000_2026.07.31.742155v3.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2010.07.004"},{"key":"2026090318103219000_2026.07.31.742155v3.2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.24.110707.175350"},{"key":"2026090318103219000_2026.07.31.742155v3.3","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar7831"},{"key":"2026090318103219000_2026.07.31.742155v3.4","first-page":"eaaz4475","article-title":"Human cohesin compacts DNA by loop extrusion. - PubMed - NCBI","volume":"47","year":"2019","journal-title":"Science"},{"key":"2026090318103219000_2026.07.31.742155v3.5","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz3418"},{"key":"2026090318103219000_2026.07.31.742155v3.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-025-00933-1"},{"key":"2026090318103219000_2026.07.31.742155v3.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)80008-8"},{"key":"2026090318103219000_2026.07.31.742155v3.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)80007-6"},{"key":"2026090318103219000_2026.07.31.742155v3.9","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/132.2.387"},{"key":"2026090318103219000_2026.07.31.742155v3.10","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(01)00271-8"},{"key":"2026090318103219000_2026.07.31.742155v3.11","doi-asserted-by":"publisher","DOI":"10.1126\/science.adw0566"},{"key":"2026090318103219000_2026.07.31.742155v3.12","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.74.082803.133219"},{"key":"2026090318103219000_2026.07.31.742155v3.13","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81019-3"},{"key":"2026090318103219000_2026.07.31.742155v3.14","doi-asserted-by":"publisher","DOI":"10.1038\/nature02742"},{"key":"2026090318103219000_2026.07.31.742155v3.15","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.151.5.1047"},{"key":"2026090318103219000_2026.07.31.742155v3.16","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80420-7"},{"key":"2026090318103219000_2026.07.31.742155v3.17","doi-asserted-by":"publisher","DOI":"10.1038\/s44318-024-00202-5"},{"key":"2026090318103219000_2026.07.31.742155v3.18","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.11315"},{"key":"2026090318103219000_2026.07.31.742155v3.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.03.017"},{"key":"2026090318103219000_2026.07.31.742155v3.20","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1093\/genetics\/151.4.1459","article-title":"Dna2 mutants reveal interactions with Dna polymerase alpha and Ctf4, a Pol alpha accessory factor, and show that full Dna2 helicase activity is not essential for growth","volume":"151","year":"1999","journal-title":"Genetics"},{"key":"2026090318103219000_2026.07.31.742155v3.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.05.036"},{"key":"2026090318103219000_2026.07.31.742155v3.22","doi-asserted-by":"publisher","DOI":"10.1038\/nature12867"},{"key":"2026090318103219000_2026.07.31.742155v3.23","doi-asserted-by":"publisher","DOI":"10.1101\/gad.350278.122"},{"key":"2026090318103219000_2026.07.31.742155v3.24","doi-asserted-by":"publisher","DOI":"10.1126\/science.1157880"},{"key":"2026090318103219000_2026.07.31.742155v3.25","doi-asserted-by":"publisher","DOI":"10.1126\/science.1157774"},{"key":"2026090318103219000_2026.07.31.742155v3.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2008.06.006"},{"key":"2026090318103219000_2026.07.31.742155v3.27","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-022-00780-0"},{"key":"2026090318103219000_2026.07.31.742155v3.28","doi-asserted-by":"crossref","unstructured":"R. E. Barton , L. F. Massari , D. Robertson , A. L. Marston , Eco1-dependent cohesin acetylation anchors chromatin loops and cohesion to define functional meiotic chromosome domains. Elife 11 (2022).","DOI":"10.7554\/eLife.74447"},{"key":"2026090318103219000_2026.07.31.742155v3.29","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-022-00773-z"},{"key":"2026090318103219000_2026.07.31.742155v3.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.09.040"},{"key":"2026090318103219000_2026.07.31.742155v3.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2006.10.061"},{"key":"2026090318103219000_2026.07.31.742155v3.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.01.025"},{"key":"2026090318103219000_2026.07.31.742155v3.33","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.17.6215"},{"key":"2026090318103219000_2026.07.31.742155v3.34","doi-asserted-by":"publisher","DOI":"10.1007\/BF02986080"},{"key":"2026090318103219000_2026.07.31.742155v3.35","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.125.3.517"},{"key":"2026090318103219000_2026.07.31.742155v3.36","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(02)70783-5"},{"key":"2026090318103219000_2026.07.31.742155v3.37","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E14-04-0929"},{"key":"2026090318103219000_2026.07.31.742155v3.38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075435"},{"key":"2026090318103219000_2026.07.31.742155v3.39","doi-asserted-by":"crossref","unstructured":"L. Costantino , T.-H. S. Hsieh , R. Lamothe , X. Darzacq , D. Koshland , Cohesin residency determines chromatin loop patterns. Elife 9 (2020).","DOI":"10.7554\/eLife.59889"},{"key":"2026090318103219000_2026.07.31.742155v3.40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0020259"},{"key":"2026090318103219000_2026.07.31.742155v3.41","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-020-0930-9"},{"key":"2026090318103219000_2026.07.31.742155v3.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.11.021"},{"key":"2026090318103219000_2026.07.31.742155v3.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.04.085"},{"key":"2026090318103219000_2026.07.31.742155v3.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.004"},{"key":"2026090318103219000_2026.07.31.742155v3.45","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201798004"},{"key":"2026090318103219000_2026.07.31.742155v3.46","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.3.307"},{"key":"2026090318103219000_2026.07.31.742155v3.47","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.3.320"},{"key":"2026090318103219000_2026.07.31.742155v3.48","doi-asserted-by":"publisher","DOI":"10.1038\/nature08550"},{"key":"2026090318103219000_2026.07.31.742155v3.49","doi-asserted-by":"crossref","unstructured":"M. Srinivasan , M. Fumasoni , N. J. Petela , A. Murray , K. A. Nasmyth , Cohesion is established during DNA replication utilising chromosome associated cohesin rings as well as those loaded de novo onto nascent DNAs. Elife 9 (2020).","DOI":"10.7554\/eLife.56611"},{"key":"2026090318103219000_2026.07.31.742155v3.50","doi-asserted-by":"publisher","DOI":"10.1093\/NAR\/GKAA541"},{"key":"2026090318103219000_2026.07.31.742155v3.51","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.9.3144-3158.2001"},{"key":"2026090318103219000_2026.07.31.742155v3.52","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.107.072876"},{"key":"2026090318103219000_2026.07.31.742155v3.53","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04759-1"},{"key":"2026090318103219000_2026.07.31.742155v3.54","first-page":"876","article-title":"FANCJ DNA helicase is recruited to the replisome by AND-1 to ensure genome stability","volume":"25","year":"2024","journal-title":"EMBO Rep"},{"key":"2026090318103219000_2026.07.31.742155v3.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.12.185"},{"key":"2026090318103219000_2026.07.31.742155v3.56","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16095-x"},{"key":"2026090318103219000_2026.07.31.742155v3.57","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-021-00783-x"},{"key":"2026090318103219000_2026.07.31.742155v3.58","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2024.08.003"},{"key":"2026090318103219000_2026.07.31.742155v3.59","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2024.02.004"},{"key":"2026090318103219000_2026.07.31.742155v3.60","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1932"},{"key":"2026090318103219000_2026.07.31.742155v3.61","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.12.038"},{"key":"2026090318103219000_2026.07.31.742155v3.62","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.04.020"},{"key":"2026090318103219000_2026.07.31.742155v3.63","doi-asserted-by":"publisher","DOI":"10.1101\/gad.349207.121"},{"key":"2026090318103219000_2026.07.31.742155v3.64","doi-asserted-by":"publisher","DOI":"10.1007\/s00412-013-0396-y"},{"key":"2026090318103219000_2026.07.31.742155v3.65","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-57530-9"},{"key":"2026090318103219000_2026.07.31.742155v3.66","doi-asserted-by":"crossref","unstructured":"P. Batty , et al., Cohesin-mediated DNA loop extrusion resolves sister chromatids in G2 phase. EMBO J. e113475 (2023).","DOI":"10.1101\/2023.01.12.523718"},{"key":"2026090318103219000_2026.07.31.742155v3.67","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2744-4"},{"key":"2026090318103219000_2026.07.31.742155v3.68","doi-asserted-by":"publisher","DOI":"10.1126\/science.adl4606"},{"key":"2026090318103219000_2026.07.31.742155v3.69","doi-asserted-by":"publisher","DOI":"10.1093\/BIOINFORMATICS\/BTZ540"},{"issue":"9","key":"2026090318103219000_2026.07.31.742155v3.70","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1038\/s41592-021-01248-7","article-title":"Systematic Evaluation of Chromosome Conformation Capture Assays","volume":"18","year":"2021","journal-title":"Nature Methods"},{"key":"2026090318103219000_2026.07.31.742155v3.71","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.117.300537"},{"key":"2026090318103219000_2026.07.31.742155v3.72","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.59889"},{"key":"2026090318103219000_2026.07.31.742155v3.73","doi-asserted-by":"publisher","DOI":"10.1038\/nature21711"},{"key":"2026090318103219000_2026.07.31.742155v3.74","doi-asserted-by":"publisher","DOI":"10.5281\/ZENODO.1490628"},{"issue":"10","key":"2026090318103219000_2026.07.31.742155v3.75","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1038\/nmeth.2148","article-title":"Iterative Correction of Hi-C Data Reveals Hallmarks of Chromosome Organization","volume":"9","year":"2012","journal-title":"Nature Methods"},{"key":"2026090318103219000_2026.07.31.742155v3.76","unstructured":"Kluyver, T. , B. Ragan-Kelley , Fernando P\u00e9rez , et al. 2016. \u201cJupyter Notebooks - a Publishing Format for Reproducible Computational Workflows.\u201d International Conference on Electronic Publishing, 87\u201390."},{"key":"2026090318103219000_2026.07.31.742155v3.77","unstructured":"Li, Heng . 2013. \u201cAligning Sequence Reads, Clone Sequences and Assembly Contigs with BWA-MEM.\u201d In arXiv [q-bio.GN]. March 16. arXiv. http:\/\/arxiv.org\/abs\/1303.3997."},{"issue":"10","key":"2026090318103219000_2026.07.31.742155v3.78","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1038\/s41592-020-0930-9","article-title":"Detecting Chromatin Interactions between and along Sister Chromatids with SisterC","volume":"17","year":"2020","journal-title":"Nature Methods"},{"key":"2026090318103219000_2026.07.31.742155v3.79","unstructured":"Open2c, N. Abdennur , and S. Abraham . 2024. \u201cCooltools: Enabling High-Resolution Hi-C Analysis in Python.\u201d PLoS Computational Biology. https:\/\/journals.plos.org\/ploscompbiol\/article?id=10.1371\/journal.pcbi.1012067."},{"issue":"5","key":"2026090318103219000_2026.07.31.742155v3.80","doi-asserted-by":"crossref","first-page":"e1012164","DOI":"10.1371\/journal.pcbi.1012164","article-title":"Pairtools: From Sequencing Data to Chromosome Contacts","volume":"20","author":"Open2C","year":"2024","journal-title":"PLoS Computational Biology"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.07.31.742155","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T01:10:44Z","timestamp":1788484244000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.07.31.742155"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,6]]},"references-count":80,"URL":"https:\/\/doi.org\/10.64898\/2026.07.31.742155","relation":{},"subject":[],"published":{"date-parts":[[2026,8,6]]},"subtype":"preprint"}}