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PMID: 9294146 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Ku70 is required for DNA repair but not for T cell antigen receptor gene recombination In vivo.

The Journal of experimental medicine ·Vol. 186 ·No. 6 ·1997-09-15 ·Pages 921-9

Ouyang H, Nussenzweig A, Kurimasa A, Soares VC, Li X, Cordon-Cardo C, Li Wh, Cheong N, Nussenzweig M, Iliakis G, Chen DJ, Li GC

Abstract

Ku is a complex of two proteins, Ku70 and Ku80, and functions as a heterodimer to bind DNA double-strand breaks (DSB) and activate DNA-dependent protein kinase. The role of the Ku70 subunit in DNA DSB repair, hypersensitivity to ionizing radiation, and V(D)J recombination was examined in mice that lack Ku70 (Ku70(-/-)). Like Ku80(-/-) mice, Ku70(-/-) mice showed a profound deficiency in DNA DSB repair and were proportional dwarfs. Surprisingly, in contrast to Ku80(-/-) mice in which both T and B lymphocyte development were arrested at an early stage, lack of Ku70 was compatible with T cell receptor gene recombination and the development of mature CD4+CD8- and CD4-CD8+ T cells. Our data shows, for the first time, that Ku70 plays an essential role in DNA DSB repair, but is not required for TCR V(D)J recombination. These results suggest that distinct but overlapping repair pathways may mediate DNA DSB repair and V(D)J recombination.

MeSH Terms
Animals Antigens, Nuclear B-Lymphocytes/cytology,immunology,metabolism Base Sequence Cell Differentiation DNA/genetics DNA Helicases DNA Primers/genetics DNA Repair/genetics,physiology DNA-Binding Proteins/genetics,metabolism Gene Rearrangement, T-Lymphocyte Gene Targeting Ku Autoantigen Mice Mice, Knockout Molecular Sequence Data Nuclear Proteins/genetics,metabolism Polymerase Chain Reaction Receptors, Antigen, T-Cell/genetics Recombination, Genetic T-Lymphocytes/cytology,immunology,metabolism
Chemicals
Antigens, Nuclear DNA Primers DNA-Binding Proteins Nuclear Proteins Receptors, Antigen, T-Cell DNA DNA Helicases XRCC5 protein, human Xrcc6 protein, human Xrcc6 protein, mouse Ku Autoantigen
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Ouyang H
Department of Medical Physics and Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York 10021, USA.
Nussenzweig A
Kurimasa A
Soares V C
Li X
Cordon-Cardo C
Li W h
Cheong N
Nussenzweig M
Iliakis G
Chen D J
Li G C
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.186.6.921
Published
1997-09-15
Pages
921-9
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2199057
Subset
IM
Grants
NCI NIH HHS · CA-42026 · United States
NCI NIH HHS · CA-56909 · United States
NCI NIH HHS · CA-31397 · United States
External Links
PubMed source DOI: 10.1084/jem.186.6.921 PMC Full Text View journal details
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