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Title: 55K isoform of CDK9 associates with Ku70 and is involved in DNA repair

Abstract

Positive elongation factor b (P-TEFb) is a cellular protein kinase that is required for RNA polymerase II (RNAP II) transcriptional elongation of protein coding genes. P-TEFb is a set of different molecular complexes, each containing CDK9 as the catalytic subunit. There are two isoforms of the CDK9 protein - the major 42 KDa CDK9 isoform and the minor 55KDa isoform that is translated from an in-frame mRNA that arises from an upstream transcriptional start site. We found that shRNA depletion of the 55K CDK9 protein in HeLa cells induces apoptosis and double-strand DNA breaks (DSBs). The levels of apoptosis and DSBs induced by the depletion were reduced by expression of a 55K CDK9 protein variant resistant to the shRNA, indicating that these phenotypes are the consequence of depletion of the 55K protein and not off-target effects. We also found that the 55K CDK9 protein, but not the 42K CDK9 protein, specifically associates with Ku70, a protein involved in DSB repair. Our findings suggest that the 55K CDK9 protein may function in repair of DNA through an association with Ku70.

Authors:
; ; ;  [1];  [2];  [1]
  1. Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030 (United States)
  2. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030 (United States)
Publication Date:
OSTI Identifier:
22202662
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 397; Journal Issue: 2; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; DNA; DNA REPAIR; GENES; HELA CELLS; MESSENGER-RNA; PHENOTYPE; POTASSIUM 55; PROTEINS

Citation Formats

Liu, Hongbing, Herrmann, Christine H., Chiang, Karen, Sung, Tzu-Ling, Moon, Sung-Hwan, Donehower, Lawrence A., Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, and Rice, Andrew P., E-mail: arice@bcm.edu. 55K isoform of CDK9 associates with Ku70 and is involved in DNA repair. United States: N. p., 2010. Web. doi:10.1016/J.BBRC.2010.05.092.
Liu, Hongbing, Herrmann, Christine H., Chiang, Karen, Sung, Tzu-Ling, Moon, Sung-Hwan, Donehower, Lawrence A., Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, & Rice, Andrew P., E-mail: arice@bcm.edu. 55K isoform of CDK9 associates with Ku70 and is involved in DNA repair. United States. https://doi.org/10.1016/J.BBRC.2010.05.092
Liu, Hongbing, Herrmann, Christine H., Chiang, Karen, Sung, Tzu-Ling, Moon, Sung-Hwan, Donehower, Lawrence A., Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, and Rice, Andrew P., E-mail: arice@bcm.edu. 2010. "55K isoform of CDK9 associates with Ku70 and is involved in DNA repair". United States. https://doi.org/10.1016/J.BBRC.2010.05.092.
@article{osti_22202662,
title = {55K isoform of CDK9 associates with Ku70 and is involved in DNA repair},
author = {Liu, Hongbing and Herrmann, Christine H. and Chiang, Karen and Sung, Tzu-Ling and Moon, Sung-Hwan and Donehower, Lawrence A. and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030 and Rice, Andrew P., E-mail: arice@bcm.edu},
abstractNote = {Positive elongation factor b (P-TEFb) is a cellular protein kinase that is required for RNA polymerase II (RNAP II) transcriptional elongation of protein coding genes. P-TEFb is a set of different molecular complexes, each containing CDK9 as the catalytic subunit. There are two isoforms of the CDK9 protein - the major 42 KDa CDK9 isoform and the minor 55KDa isoform that is translated from an in-frame mRNA that arises from an upstream transcriptional start site. We found that shRNA depletion of the 55K CDK9 protein in HeLa cells induces apoptosis and double-strand DNA breaks (DSBs). The levels of apoptosis and DSBs induced by the depletion were reduced by expression of a 55K CDK9 protein variant resistant to the shRNA, indicating that these phenotypes are the consequence of depletion of the 55K protein and not off-target effects. We also found that the 55K CDK9 protein, but not the 42K CDK9 protein, specifically associates with Ku70, a protein involved in DSB repair. Our findings suggest that the 55K CDK9 protein may function in repair of DNA through an association with Ku70.},
doi = {10.1016/J.BBRC.2010.05.092},
url = {https://www.osti.gov/biblio/22202662}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 2,
volume = 397,
place = {United States},
year = {Fri Jun 25 00:00:00 EDT 2010},
month = {Fri Jun 25 00:00:00 EDT 2010}
}