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Updated: Jul 1, 2025

Author Spotlight: Visualizing Single-Stranded DNA During DNA Repair for Therapeutic Insights
Published on: December 22, 2023
CDK9-55 guides the anaphase-promoting complex/cyclosome (APC/C) in choosing the DNA repair pathway choice
Luigi Alfano1, Carmelina Antonella Iannuzzi2, Daniela Barone2
1Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Fondazione G. Pascale, Napoli, Italy. l.alfano@istitutotumori.na.it.
None:
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. Mutated non-phosphorylatable CDC23(S588A) affected the repair pathway choice by impairing HR and favouring error-prone NHEJ. This CDK9 role should be considered when designing CDK-inhibitor-based cancer therapies.
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