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Cell Rep. 2015 Dec 15;13(10):2056-63. doi: 10.1016/j.celrep.2015.11.015. Epub 2015 Dec 6.

CDK1 Enhances Mitochondrial Bioenergetics for Radiation-Induced DNA Repair.

Author information

1
Department of Radiation Oncology, National Cancer Institute-Designated Comprehensive Cancer Center, University of California Davis School of Medicine, Sacramento, CA 95817, USA.
2
Department of Medical Microbiology and Immunology, University of California Davis, Davis, CA 95616, USA.
3
Departments of Biochemistry and Molecular Medicine and Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Davis, CA 95616, USA.
4
Department of Radiation Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
5
Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL 60637, USA.
6
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.

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.

KEYWORDS:

CDK1; DNA repair; mitochondrial bioenergetics; radiation

PMID:
26670043
PMCID:
PMC4684969
DOI:
10.1016/j.celrep.2015.11.015
[Indexed for MEDLINE]
Free PMC Article

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