title: CDK1 Enhances Mitochondrial Bioenergetics for Radiation-Induced DNA Repair.
abstract: Nuclear DNA repair capacity is a critical determinant of cell fate under genotoxic stress conditions. DNA repair is a well-defined energy-consuming process. However, it is unclear how DNA repair is fueled and whether mitochondrial energy production contributes to nuclear DNA repair. Here, we report a dynamic enhancement of oxygen consumption and mitochondrial ATP generation in irradiated normal cells, paralleled with increased mitochondrial relocation of the cell-cycle kinase CDK1 and nuclear DNA repair. The basal and radiation-induced mitochondrial ATP generation is reduced significantly in cells harboring CDK1 phosphorylation-deficient mutant complex I subunits. Similarly, mitochondrial ATP generation and nuclear DNA repair are also compromised severely in cells harboring mitochondrially targeted, kinase-deficient CDK1. These results demonstrate a mechanism governing the communication between mitochondria and the nucleus by which CDK1 boosts mitochondrial bioenergetics to meet the increased cellular fuel demand for DNA repair and cell survival under genotoxic stress conditions.
authors.affiliation: Department of Radiation Oncology, National Cancer Institute-Designated Comprehensive Cancer Center, University of California Davis School of Medicine, Sacramento, CA 95817, USA.
authors.forename: Lili
authors.initials: L
authors.lastname: Qin
authors.affiliation: Department of Radiation Oncology, National Cancer Institute-Designated Comprehensive Cancer Center, University of California Davis School of Medicine, Sacramento, CA 95817, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Fan
authors.affiliation: Department of Radiation Oncology, National Cancer Institute-Designated Comprehensive Cancer Center, University of California Davis School of Medicine, Sacramento, CA 95817, USA.
authors.forename: Demet
authors.initials: D
authors.lastname: Candas
authors.affiliation: Department of Medical Microbiology and Immunology, University of California Davis, Davis, CA 95616, USA.
authors.forename: Guochun
authors.initials: G
authors.lastname: Jiang
authors.affiliation: Departments of Biochemistry and Molecular Medicine and Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Davis, CA 95616, USA.
authors.forename: Stelios
authors.initials: S
authors.lastname: Papadopoulos
authors.affiliation: Departments of Biochemistry and Molecular Medicine and Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Davis, CA 95616, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Radiation Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Gayle
authors.initials: G
authors.lastname: Woloschak
authors.affiliation: Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Grdina
authors.affiliation: Department of Radiation Oncology, National Cancer Institute-Designated Comprehensive Cancer Center, University of California Davis School of Medicine, Sacramento, CA 95817, USA. Electronic address: jijli@ucdavis.edu.
authors.forename: Jian Jian
authors.initials: JJ
authors.lastname: Li
mesh_terms: D000255:Adenosine Triphosphate; D015153:Blotting, Western; D016203:CDC2 Protein Kinase; D002460:Cell Line; D020552:Comet Assay; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004249:DNA Damage / Q000502:physiology* / Q000528:radiation effects; D004260:DNA Repair / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology; D055785:Gene Knockdown Techniques; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D021381:Protein Transport / Q000528:radiation effects; D034741:RNA, Small Interfering; D011830:Radiation Effects; D014162:Transfection
chemical_list: D034741:RNA, Small Interfering; D000255:Adenosine Triphosphate; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases
keywords: CDK1; DNA repair; mitochondrial bioenergetics; radiation