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Homologous recombination (HR) is a high-fidelity DSB repair pathway that copies the sequence spanning the break from a homologous template, but how DNA ends are held together during HR remains unclear. Here we demonstrate that the proline-serine-threonine (PST) repeat region of Mediator of DNA Damage Checkpoint 1 (MDC1) is a multivalent nucleosome-binding domain, sufficient to tether chromatin in multiple contexts. In interphase, the constitutive chromatin association of MDC1 is critical for RAD51 loading and efficient HR. In mitosis, PST-mediated chromatin binding is attenuated by phosphorylation, preventing aberrant chromosomal interactions while preserving DNA tethering by the MDC1\u2013TOPBP1\u2013CIP2A complex. In total, this work demonstrates that the PST repeat region of MDC1 is a multivalent nucleosome-binding domain with tunable affinity that supports DSB repair by HR and maintains genome stability during mitosis.<\/jats:p>","DOI":"10.1093\/nar\/gkag866","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:18:19Z","timestamp":1788520699000},"source":"Crossref","is-referenced-by-count":0,"title":["Dynamic chromatin tethering of MDC1 regulates genome stability"],"prefix":"10.1093","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0847-0501","authenticated-orcid":false,"given":"Joshua R","family":"Heyza","sequence":"first","affiliation":[{"name":"Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing,MI 48824 ,","place":["United States"]},{"name":"Department of Pharmacology, Wayne State University School of Medicine , Detroit, MI 48202 ,","place":["United States"]},{"name":"Institute of 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