{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:01:22Z","timestamp":1790002882092,"version":"4.0.1"},"posted":{"date-parts":[[2026,9,17]]},"group-title":"Molecular Biology","reference-count":59,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["R35 GM127029"],"award-info":[{"award-number":["R35 GM127029"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32 GM139798"],"award-info":[{"award-number":["T32 GM139798"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  In budding yeast, the DNA damage checkpoint kinase Mec1\n                  <jats:sup>ATR<\/jats:sup>\n                  is the primary sensor of DSB-associated single-stranded DNA and coordinates cell cycle arrest with DNA repair. Deletion of Mec1 completely abolishes G2\/M cell cycle arrest; however, approximately half of\n                  <jats:italic>mec1<\/jats:italic>\n                  \u0394 cells still survive an endonuclease-induced DSB, repairing the DSB either by single-strand annealing or break-induced replication. Here we show that Mec1-independent DSB repair is independent of Rad9 but requires the Tel1\n                  <jats:sup>ATM<\/jats:sup>\n                  kinase, Rad53 kinase, and the 9-1-1 sliding clamp, which promotes Tel1 retention at damage sites. We identify Mrc1\n                  <jats:sup>Claspin<\/jats:sup>\n                  , a replication fork-associated checkpoint mediator, as an unexpected contributor to DSB survival in the absence of Mec1. Unlike Rad9, the canonical DNA damage adaptor, Mrc1\u2019s role in DSB survival is independent of its Mec1\/Tel1 consensus phosphorylation sites and relies primarily on its C-terminal domain. Mrc1 accumulates at a single DSB and both promotes end-tethering and limits DNA end-resection in an S-phase-specific manner. Mrc1 functions independently of its replication checkpoint partners, Tof1 and Csm3. We further show that heterochromatic gene silencing in budding yeast is Mrc1-dependent but Tof1\u2013 and Csm3-independent. Together, these findings define a Mec1-independent survival pathway and establish Mrc1 as a novel regulator of DSB repair.\n                <\/jats:p>","DOI":"10.64898\/2026.09.15.751834","type":"posted-content","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:00:24Z","timestamp":1789671624000},"source":"Crossref","is-referenced-by-count":0,"title":["Replication Fork-Associated Checkpoint Mediator Mrc1\/Claspin Acts in Arrest-Independent Double-Strand Break Survival"],"prefix":"10.64898","author":[{"given":"Marissa M.","family":"Ashton","sequence":"first","affiliation":[{"name":"Department of Biology and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02453, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliot","family":"Busch","sequence":"additional","affiliation":[{"name":"Department of Biology and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02453, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1878-0610","authenticated-orcid":false,"given":"James E.","family":"Haber","sequence":"additional","affiliation":[{"name":"Department of Biology and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02453, 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