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Its role in Okazaki fragment processing has been proposed to explain why <jats:italic>DNA2<\/jats:italic> is indispensable for cell survival across organisms. Unexpectedly, we found that <jats:italic>DNA2<\/jats:italic> has an essential role in suppressing homologous recombination (HR)-dependent replication restart at stalled RFs. In the absence of <jats:italic>DNA2<\/jats:italic>-mediated RF recovery, excessive HR-restart of stalled RFs results in toxic levels of abortive recombination intermediates that lead to DNA damage-checkpoint activation and terminal cell-cycle arrest. While HR proteins protect and restart stalled RFs to promote faithful genome replication, these findings show how HR-dependent replication restart is actively constrained by <jats:italic>DNA2<\/jats:italic> to ensure cell survival. These new insights disambiguate the effects of <jats:italic>DNA2<\/jats:italic> dysfunction on cell survival, and provide a framework to rationalize the association of <jats:italic>DNA2<\/jats:italic> with cancer and the primordial dwarfism disorder Seckel syndrome based on its role in RF recovery.<\/jats:p>","DOI":"10.1007\/s00294-020-01106-7","type":"journal-article","created":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T14:02:07Z","timestamp":1599746527000},"page":"1085-1092","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Limiting homologous recombination at stalled replication forks is essential for cell viability: DNA2 to the rescue"],"prefix":"10.1007","volume":"66","author":[{"given":"Rowin","family":"Appanah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beno\u00eet","family":"Falquet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9275-9062","authenticated-orcid":false,"given":"Ulrich","family":"Rass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,9]]},"reference":[{"key":"1106_CR1","doi-asserted-by":"publisher","first-page":"2011","DOI":"10.1038\/sj.emboj.7600670","volume":"24","author":"JS Ahn","year":"2005","unstructured":"Ahn JS, Osman F, Whitby MC (2005) Replication fork blockage by RTS1 at an ectopic site promotes recombination in fission yeast. 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