Dbf4-dependent kinase promotes cell cycle controlled resection of DNA double-strand breaks and repair by homologous recombination

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dc.contributor.authorGalanti, Lorenzo
dc.contributor.authorPeritore, Martina
dc.contributor.authorGnügge, Robert
dc.contributor.authorCannavo, Elda
dc.contributor.authorHeipke, Johannes
dc.contributor.authorPalumbieri, Maria Dilia
dc.contributor.authorSteigenberger, Barbara
dc.contributor.authorSymington, Lorraine S.
dc.contributor.authorCejka, Petr
dc.contributor.authorPfander, Boris
dc.date.accessioned2024-09-02T11:58:02Z
dc.date.available2024-09-02T11:58:02Z
dc.date.issued2024-04-03
dc.description.abstractDNA double-strand breaks (DSBs) can be repaired by several pathways. In eukaryotes, DSB repair pathway choice occurs at the level of DNA end resection and is controlled by the cell cycle. Upon cell cycle-dependent activation, cyclin-dependent kinases (CDKs) phosphorylate resection proteins and thereby stimulate end resection and repair by homologous recombination (HR). However, inability of CDK phospho-mimetic mutants to bypass this cell cycle regulation, suggests that additional cell cycle regulators may be important. Here, we identify Dbf4-dependent kinase (DDK) as a second major cell cycle regulator of DNA end resection. Using inducible genetic and chemical inhibition of DDK in budding yeast and human cells, we show that end resection and HR require activation by DDK. Mechanistically, DDK phosphorylates at least two resection nucleases in budding yeast: the Mre11 activator Sae2, which promotes resection initiation, as well as the Dna2 nuclease, which promotes resection elongation. Notably, synthetic activation of DDK allows limited resection and HR in G1 cells, suggesting that DDK is a key component of DSB repair pathway selection.en
dc.identifier.urihttp://hdl.handle.net/2003/42666
dc.identifier.urihttp://dx.doi.org/10.17877/DE290R-24502
dc.language.isoende
dc.relation.ispartofseriesNature communications;15
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/de
dc.subjectDNAen
dc.subjectDNA recombinationen
dc.subjectDouble-strand DNA breaksen
dc.subjectKinasesen
dc.subjectPhosphorylationen
dc.subject.ddc540
dc.titleDbf4-dependent kinase promotes cell cycle controlled resection of DNA double-strand breaks and repair by homologous recombinationen
dc.typeTextde
dc.type.publicationtypeArticlede
dcterms.accessRightsopen access
eldorado.secondarypublicationtruede
eldorado.secondarypublication.primarycitationGalanti, L., Peritore, M., Gnügge, R. et al. Dbf4-dependent kinase promotes cell cycle controlled resection of DNA double-strand breaks and repair by homologous recombination. Nat Commun 15, 2890 (2024). https://doi.org/10.1038/s41467-024-46951-zde
eldorado.secondarypublication.primaryidentifierhttps://doi.org/10.1038/s41467-024-46951-zde

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Fakultät für Chemie und Chemische Biologie