{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:00:52Z","timestamp":1790913652203,"version":"4.1.0"},"reference-count":159,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T00:00:00Z","timestamp":1618272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The conserved nuclease-helicase DNA2 has been linked to mitochondrial myopathy, Seckel syndrome, and cancer. Across species, the protein is indispensable for cell proliferation. On the molecular level, DNA2 has been implicated in DNA double-strand break (DSB) repair, checkpoint activation, Okazaki fragment processing (OFP), and telomere homeostasis. More recently, a critical contribution of DNA2 to the replication stress response and recovery of stalled DNA replication forks (RFs) has emerged. Here, we review the available functional and phenotypic data and propose that the major cellular defects associated with DNA2 dysfunction, and the links that exist with human disease, can be rationalized through the fundamental importance of DNA2-dependent RF recovery to genome duplication. Being a crucial player at stalled RFs, DNA2 is a promising target for anti-cancer therapy aimed at eliminating cancer cells by replication-stress overload.<\/jats:p>","DOI":"10.3390\/ijms22083984","type":"journal-article","created":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T05:31:37Z","timestamp":1618291897000},"page":"3984","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["DNA2 in Chromosome Stability and Cell Survival\u2014Is It All about Replication Forks?"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3189-2622","authenticated-orcid":false,"given":"Jessica J. R.","family":"Hudson","sequence":"first","affiliation":[{"name":"Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9275-9062","authenticated-orcid":false,"given":"Ulrich","family":"Rass","sequence":"additional","affiliation":[{"name":"Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6465","DOI":"10.1073\/pnas.80.21.6465","article-title":"Isolation of yeast DNA replication mutants in permeabilized cells","volume":"80","author":"Kuo","year":"1983","journal-title":"Proc. Natl. Acad. Sci. 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