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Ca\n                    <jats:sup>2+<\/jats:sup>\n                    binding to Calmodulin induces a conformational change that facilitates interaction with, and activation of, serine\/threonine protein kinases, including members of the CaMK family. Recently, Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010Calmodulin binding to one such protein kinase, Checkpoint kinase 2 (CHK2), which is responsible for the regulation of cell cycle progression following DNA damage in mammalian cells, was shown to suppress CHK2 catalytic activity. Here, by applying biochemical, structural mass spectrometry and yeast genetic methods, we identify an analogous mode of inhibition of the fission yeast\n                    <jats:italic>Schizosaccharomyces pombe<\/jats:italic>\n                    CHK2 functional orthologue, Cds1, through direct binding of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010Calmodulin to the Cds1 kinase domain. Our studies assert an ancestral function for Calmodulin in suppressing the catalytic activity of CHK2 orthologs and highlight a mechanism by which Ca\n                    <jats:sup>2+<\/jats:sup>\n                    flux can attenuate Cds1 catalytic activity to facilitate exit from the replication checkpoint and promote cell cycle progression.\n                  <\/jats:p>","DOI":"10.1002\/iub.70128","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:08:07Z","timestamp":1787807287000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Ancestral Mechanism of Calmodulin Binding to Cds1 Kinase Inhibits Catalytic Activity"],"prefix":"10.1002","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1414-9830","authenticated-orcid":false,"given":"Stephanie A.","family":"Manovella","sequence":"first","affiliation":[{"name":"Drug Discovery Biology Monash Institute of Pharmaceutical Sciences, Monash University  Melbourne Victoria Australia"},{"name":"Walter and Eliza Hall Institute of Medical Research  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7739-4787","authenticated-orcid":false,"given":"Tingting","family":"Wang","sequence":"additional","affiliation":[{"name":"Flinders Health and Medical Research Institute, Flinders University  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6543-1851","authenticated-orcid":false,"given":"Samuel N.","family":"Young","sequence":"additional","affiliation":[{"name":"Walter and Eliza Hall Institute of Medical Research  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toby A.","family":"Dite","sequence":"additional","affiliation":[{"name":"Walter and Eliza Hall Institute of Medical Research  Parkville Victoria Australia"},{"name":"Department of Medical Biology University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vineet","family":"Vaibhav","sequence":"additional","affiliation":[{"name":"Walter and Eliza Hall Institute of Medical Research  Parkville Victoria Australia"},{"name":"Department of Medical Biology University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Binos","sequence":"additional","affiliation":[{"name":"Walter and Eliza Hall Institute of Medical Research  Parkville Victoria Australia"},{"name":"Department of Medical Biology University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4171-3712","authenticated-orcid":false,"given":"Laura F.","family":"Dagley","sequence":"additional","affiliation":[{"name":"Walter and Eliza Hall Institute of Medical Research  Parkville Victoria Australia"},{"name":"Department of Medical Biology University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6385-0585","authenticated-orcid":false,"given":"Anh T. 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