Format

Send to

Choose Destination
Immunity. 1998 Sep;9(3):367-76.

A targeted DNA-PKcs-null mutation reveals DNA-PK-independent functions for KU in V(D)J recombination.

Author information

1
Howard Hughes Medical Institute, The Children's Hospital, The Center for Blood Research and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.

Abstract

The DNA-dependent protein kinase (DNA-PK) consists of Ku70, Ku80, and a large catalytic subunit, DNA-PKcs. Targeted inactivation of the Ku70 or Ku80 genes results in elevated ionizing radiation (IR) sensitivity and inability to perform both V(D)J coding-end and signal (RS)-end joining in cells, with severe growth retardation plus immunodeficiency in mice. In contrast, we now demonstrate that DNA-PKcs-null mice generated by gene-targeted mutation, while also severely immunodeficient, exhibit no growth retardation. Furthermore, DNA-PKcs-null cells are blocked for V(D)J coding-end joining, but retain normal RS-end joining. Finally, while DNA-PK-null fibroblasts exhibited increased IR sensitivity, DNA-PKcs-deficient ES cells did not. We conclude that Ku70 and Ku80 may have functions in V(D)J recombination and DNA repair that are independent of DNA-PKcs.

PMID:
9768756
DOI:
10.1016/s1074-7613(00)80619-6
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center