{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:29:14Z","timestamp":1790958554072,"version":"4.1.0"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"19","license":[{"start":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T00:00:00Z","timestamp":1724803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018554","name":"New York Institute of Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018554","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chromosome instability (CIN) is frequently observed in many tumors. The breakage-fusion-bridge (BFB) cycle has been proposed to be one of the main drivers of CIN during tumorigenesis and tumor evolution. However, the detailed mechanism\u00a0for the individual steps of the BFB cycle warrants further investigation. Here, we demonstrate\u00a0that a nuclease-dead Cas9 (dCas9) coupled with a telomere-specific single-guide RNA (sgTelo) can be used to model the BFB cycle. First, we show\u00a0that targeting dCas9 to telomeres using sgTelo impedes\u00a0DNA replication at telomeres and induces\u00a0a pronounced increase of replication stress and DNA damage. Using Single-Molecule Telomere Assay via Optical Mapping (SMTA-OM), we investigate\u00a0the genome-wide features of telomeres in the dCas9\/sgTelo cells and observe\u00a0a dramatic increase of chromosome end fusions, including fusion\/ITS+\u00a0and fusion\/ITS\u2212. Consistently, we also observe\u00a0an increase in the formation of dicentric chromosomes, anaphase bridges, and intercellular telomeric chromosome bridges (ITCBs). Utilizing the dCas9\/sgTelo system, we uncover\u00a0many interesting molecular and structural features of the ITCB and demonstrate\u00a0that multiple DNA repair pathways are implicated in the formation of ITCBs. Our studies shed new light on the molecular mechanisms of the BFB cycle, which will advance our understanding of tumorigenesis, tumor evolution, and drug resistance.<\/jats:p>","DOI":"10.1093\/nar\/gkae747","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T10:32:47Z","timestamp":1724841167000},"page":"11689-11703","source":"Crossref","is-referenced-by-count":5,"title":["Elucidation of the molecular mechanism of the breakage-fusion-bridge (BFB) cycle using a CRISPR-dCas9 cellular model"],"prefix":"10.1093","volume":"52","author":[{"given":"Manrose","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, College of Osteopathic Medicine, New York Institute of Technology , Old Westbury, NY\u00a0 11568 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlin","family":"Raseley","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Science and Health System, Drexel University , Philadelphia , PA 19104 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis\u00a0M","family":"Perez","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Osteopathic Medicine, New York Institute of Technology , Old Westbury, NY\u00a0 11568 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny","family":"MacKenzie","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Osteopathic Medicine, New York Institute of Technology , Old Westbury, NY\u00a0 11568 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Settapong\u00a0T","family":"Kosiyatrakul","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Albert Einstein College of Medicine , Bronx , NY\u00a0 10461 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