Luigi Alfano, Carmelina Antonella Iannuzzi, Daniela Barone, Iris Maria Forte, Maria Carmen Ragosta, Maria Cuomo, Giulio Mazzarotti, Milena Dell'Aquila, Angela Altieri, Antonella Caporaso, Cristin Roma, Laura Marra, Silvia Boffo, Paola Indovina, Michelino De Laurentiis, Antonio Giordano
DNA double-strand breaks (DSBs) contribute to genome instability, a key feature of cancer. DSBs are mainly repaired by homologous recombination (HR) and non-homologous end-joining (NHEJ). We investigated the role of an isoform of the multifunctional cyclin-dependent kinase 9, CDK9-55, in DNA repair, by generating CDK9-55-knockout HeLa clones (through CRISPR-Cas9), which showed potential HR dysfunction. A phosphoproteomic screening in these clones treated with camptothecin revealed that CDC23 (cell division cycle 23), a component of the E3-ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome), is a new substrate of CDK9-55, with S588 being its putative phosphorylation site...
March 4, 2024: Oncogene