CDK1 Enhances Mitochondrial Bioenergetics for Radiation-Induced DNA Repair

Qin, Lili; Fan, Ming; Candas, Demet; Jiang, Guochun; Papadopoulos, Stelios; Tian, Lin; Woloschak, Gayle; Grdina, David J.; Li, Jian Jian

doi:10.1016/j.celrep.2015.11.015

Title: CDK1 Enhances Mitochondrial Bioenergetics for Radiation-Induced DNA Repair

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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 findings 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:: Qin, Lili; Fan, Ming; Candas, Demet; Jiang, Guochun; Papadopoulos, Stelios; Tian, Lin; Woloschak, Gayle; Grdina, David J.; Li, Jian Jian

Publication Date:: Tue Dec 01 00:00:00 EST 2015

Research Org.:: Northwestern Univ., Chicago, IL (United States)

Sponsoring Org.:: USDOE Office of Science (SC)

OSTI Identifier:: 1242318

Alternate Identifier(s):: OSTI ID: 1240128

Grant/Contract Number:: SC0001271

Resource Type:: Published Article

Journal Name:: Cell Reports

Additional Journal Information:: Journal Name: Cell Reports Journal Volume: 13 Journal Issue: 10; Journal ID: ISSN 2211-1247

Publisher:: Elsevier

Country of Publication:: Netherlands

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES; CDK1; mitochondrial bioenergetics; DNA repair; radiation

Citation Formats


                    Qin, Lili, Fan, Ming, Candas, Demet, Jiang, Guochun, Papadopoulos, Stelios, Tian, Lin, Woloschak, Gayle, Grdina, David J., and Li, Jian Jian. CDK1 Enhances Mitochondrial Bioenergetics for Radiation-Induced DNA Repair.  Netherlands: N. p., 2015. 
Web.  doi:10.1016/j.celrep.2015.11.015.

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                    Qin, Lili, Fan, Ming, Candas, Demet, Jiang, Guochun, Papadopoulos, Stelios, Tian, Lin, Woloschak, Gayle, Grdina, David J., & Li, Jian Jian. CDK1 Enhances Mitochondrial Bioenergetics for Radiation-Induced DNA Repair.  Netherlands.  https://doi.org/10.1016/j.celrep.2015.11.015

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                    Qin, Lili, Fan, Ming, Candas, Demet, Jiang, Guochun, Papadopoulos, Stelios, Tian, Lin, Woloschak, Gayle, Grdina, David J., and Li, Jian Jian. Tue .  
"CDK1 Enhances Mitochondrial Bioenergetics for Radiation-Induced DNA Repair".  Netherlands.  https://doi.org/10.1016/j.celrep.2015.11.015.

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@article{osti_1242318,

  title        = {CDK1 Enhances Mitochondrial Bioenergetics for Radiation-Induced DNA Repair},

  author       = {Qin, Lili and Fan, Ming and Candas, Demet and Jiang, Guochun and Papadopoulos, Stelios and Tian, Lin and Woloschak, Gayle and Grdina, David J. and Li, Jian Jian},

  abstractNote = {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 findings 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.},

  doi          = {10.1016/j.celrep.2015.11.015},

  journal      = {Cell Reports},

  number       = 10,

  volume       = 13,

  place        = {Netherlands},

  year         = {Tue Dec 01 00:00:00 EST 2015},

  month        = {Tue Dec 01 00:00:00 EST 2015}

}

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