{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:12:06Z","timestamp":1790745126299,"version":"4.1.0"},"reference-count":144,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T00:00:00Z","timestamp":1605571200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T00:00:00Z","timestamp":1605571200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T00:00:00Z","timestamp":1605571200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM11755"],"award-info":[{"award-number":["R01GM11755"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21OD023720"],"award-info":[{"award-number":["R21OD023720"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R03NS106486"],"award-info":[{"award-number":["R03NS106486"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007880","name":"Johns Hopkins University","doi-asserted-by":"publisher","award":["Catalyst Award"],"award-info":[{"award-number":["Catalyst Award"]}],"id":[{"id":"10.13039\/100007880","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["T32CA009110"],"award-info":[{"award-number":["T32CA009110"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Mutations of SMC5\/6 components cause developmental defects, including primary microcephaly. To model neurodevelopmental defects, we engineered a mouse wherein\n                    <jats:italic>Smc5<\/jats:italic>\n                    is conditionally knocked out (cKO) in the developing neocortex.\n                    <jats:italic>Smc5<\/jats:italic>\n                    cKO mice exhibited neurodevelopmental defects due to neural progenitor cell (NPC) apoptosis, which led to reduction in cortical layer neurons.\n                    <jats:italic>Smc5<\/jats:italic>\n                    cKO NPCs formed DNA bridges during mitosis and underwent chromosome missegregation. SMC5\/6 depletion triggers a CHEK2-p53 DNA damage response, as concomitant deletion of the\n                    <jats:italic>Trp53<\/jats:italic>\n                    tumor suppressor or\n                    <jats:italic>Chek2<\/jats:italic>\n                    DNA damage checkpoint kinase rescued\n                    <jats:italic>Smc5<\/jats:italic>\n                    cKO neurodevelopmental defects. Further assessment using\n                    <jats:italic>Smc5<\/jats:italic>\n                    cKO and auxin-inducible degron systems demonstrated that absence of SMC5\/6 leads to DNA replication stress at late-replicating regions such as pericentromeric heterochromatin. In summary, SMC5\/6 is important for completion of DNA replication prior to entering mitosis, which ensures accurate chromosome segregation. Thus, SMC5\/6 functions are critical in highly proliferative stem cells during organism development.\n                  <\/jats:p>","DOI":"10.7554\/elife.61171","type":"journal-article","created":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T08:00:31Z","timestamp":1605600031000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.61171","source":"Crossref","is-referenced-by-count":35,"title":["SMC5\/6 is required for replication fork stability and faithful chromosome segregation during neurogenesis"],"prefix":"10.7554","volume":"9","author":[{"given":"Alisa","family":"Atkins","sequence":"first","affiliation":[{"name":"Biochemistry and Molecular Biology Department, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle J","family":"Xu","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Department, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1047-1554","authenticated-orcid":true,"given":"Maggie","family":"Li","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Department, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0411-5249","authenticated-orcid":true,"given":"Nathaniel P","family":"Rogers","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Department, Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3462-5768","authenticated-orcid":true,"given":"Marina V","family":"Pryzhkova","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology 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