{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:35:17Z","timestamp":1787567717200,"version":"build-2736575974"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"16","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Joint Innovation Team for Clinical & Basic Research","award":["202410"],"award-info":[{"award-number":["202410"]}]},{"DOI":"10.13039\/501100015508","name":"Shandong Academy of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100015508","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2024MC179"],"award-info":[{"award-number":["ZR2024MC179"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>L Antigen Family Member 3 (LAGE3) is a core component of the KEOPS complex, mutations of which are implicated in Galloway\u2013Mowat syndrome (GAMOS). The KEOPS complex is known to function in telomere maintenance and tRNA N6-threonylcarbamoyladenosine (t6A) modification. However, whether the KEOPS complex also contributes to chromosomal DNA regulation through additional mechanisms remains elusive. Here, we find that LAGE3 and the other four components of KEOPS localize to the stalled forks and protect the nascent DNA strand from degradation under DNA replication stress. TurboID-mediated proximity labeling identifies the MRE11 nuclease as a LAGE3-interacting partner, and LAGE3 deficiency leads to unscheduled stalled forks degradation in an MRE11 nuclease-dependent manner. Similarly, TP53RK, another KEOPS subunit, also exhibits a protective role at stalled forks. In vitro experiments demonstrate that the KEOPS complex prefers to bind to a ds-ssDNA junction, then directly limits MRE11 to degrade nascent DNA. In addition, GAMOS-associated LAGE3 mutations disrupt KEOPS complex assembly, preventing its recruitment to stalled replication forks and consequently leading to unscheduled fork resection and genome instability under DNA replication stress. Collectively, our findings reveal that LAGE3 acts as a stalled fork protector to prevent genome instability during DNA replication stress, providing new insights into GAMOS pathogenesis.<\/jats:p>","DOI":"10.1093\/nar\/gkag842","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T11:18:12Z","timestamp":1786706292000},"source":"Crossref","is-referenced-by-count":0,"title":["L Antigen Family Member 3 stabilizes stalled replication forks by reducing MRE11 resection to maintain genome stability"],"prefix":"10.1093","volume":"54","author":[{"given":"Meng","family":"Lyu","sequence":"first","affiliation":[{"name":"Dermatology Hospital of Shandong First Medical University , Jinan, Shandong 250022 ,","place":["P.R. China"]},{"name":"Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences , Jinan, Shandong 250022 ,","place":["P.R. China"]},{"name":"School of Clinical and Basic Medical Sciences, Shandong First Medical University and Shandong Academy of Medical Sciences , Jinan, Shandong 250117 ,","place":["P.R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guihua","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Clinical and Basic Medical Sciences, Shandong First Medical University and Shandong Academy of Medical Sciences , Jinan, Shandong 250117 ,","place":["P.R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaopeng","family":"Jia","sequence":"additional","affiliation":[{"name":"School of Clinical and Basic Medical Sciences, Shandong First Medical University and Shandong Academy of Medical Sciences , Jinan, Shandong 250117 ,","place":["P.R. 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