The Absence of the DNA-Dependent Protein Kinase Catalytic Subunit in Mice Results in Anaphase Bridges and in Increased Telomeric Fusions with Normal Telomere Length and G-Strand Overhang

doi:10.1128/MCB.21.11.3642-3651.2001

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Molecular and Cellular Biology, June 2001, p. 3642-3651, Vol. 21, No. 11
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.11.3642-3651.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

The Absence of the DNA-Dependent Protein Kinase Catalytic Subunit in Mice Results in Anaphase Bridges and in Increased Telomeric Fusions with Normal Telomere Length and G-Strand Overhang

Fermín A. Goytisolo,¹ Enrique Samper,¹ Scott Edmonson,² Guillermo E. Taccioli,² and María A. Blasco¹^,^*

Department of Immunology and Oncology, Centro Nacional de Biotecnología, Madrid E-28049, Spain,¹ and Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts 02118-2526²

Received 2 November 2000/Returned for modification 11 December 2000/Accepted 23 February 2001

The major pathway in mammalian cells for repairing DNA double-strand breaks (DSB) is via nonhomologous end joining. Five componentsfunction in this pathway, of which three (Ku70, Ku80, and theDNA-dependent protein kinase catalytic subunit [DNA-PKcs]) constitutea complex termed DNA-dependent protein kinase (DNA-PK). MammalianKu proteins bind to DSB and recruit DNA-PKcs to the break. Interestingly,besides their role in DSB repair, Ku proteins bind to chromosomeends, or telomeres, protecting them from end-to-end fusions. Herewe show that DNA-PKcs^/ cells display an increased frequency of spontaneous telomericfusions and anaphase bridges. However, DNA-PKcs deficiency doesnot result in significant changes in telomere length or in deregulationof the G-strand overhang at the telomeres. Although less severe,this phenotype is reminiscent of the one recently described forKu86-defective cells. Here we show that, besides DNA repair, arole for DNA-PKcs is to protect telomeres, which in turn are essentialfor chromosomalstability.

^* Corresponding author. Mailing address: Department of Immunology and Oncology, Centro Nacional de Biotecnología, Madrid E-28049,Spain. Phone: 34-915854846. Fax: 34-913720493. E-mail: mblasco{at}cnb.uam.es.

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