skip to main content

This content will become publicly available on November 5, 2015

Title: CDK1 enhances mitochondrial bioenergetics for radiation-induced DNA repair

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:
 [1] ;  [1] ;  [1] ;  [2] ;  [3] ;  [3] ;  [4] ;  [5] ;  [1]
  1. Univ. of California Davis School of Medicine, Sacramento, CA (United States)
  2. Univ. of California, Davis, CA (United States)
  3. Univ. of California Davis School of Medicine, Davis, CA (United States)
  4. Northwestern Univ., Chicago, IL (United States)
  5. Univ. of Chicago, Chicago, IL (United States)
Publication Date:
OSTI Identifier:
1242318
Grant/Contract Number:
SC0001271
Type:
Published Article
Journal Name:
Cell Reports
Additional Journal Information:
Journal Volume: 13; Journal Issue: 10; Journal ID: ISSN 2211-1247
Publisher:
Elsevier
Research Org:
Northwestern Univ., Chicago, IL (United States)
Sponsoring Org:
USDOE Office of Science (SC)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; CDK1; mitochondrial bioenergetics; DNA repair; radiation