Complementation of the ionizing radiation sensitivity, DNA end binding, and V(D)J recombination defects of double-strand break repair mutants by the p86 Ku autoantigen.
Two ionizing radiation-sensitive (IRs) and DNA double-strand break (DSB) mutants, sxi-3 and sxi-2, were shown to be severely deficient in a DNA end binding activity, similar to a previously described activity of the Ku autoantigen, correlating with the xrs (XRCC5) mutations. Cell fusions with xrs-6, another IRs, DSB repair-deficient cell line, defined these sxi mutants in the XRCC5 group. sxi-3 cells have low expression levels of the p86Ku mRNA. Introduction of the Ku p86 gene, but not the p70 Ku gene, complemented the IRs, DNA end binding, and variable (diversity) joining [V(D)J] recombination signal and coding junction deficiencies of sxi-3. Thus, the p86 Ku gene product is essential for DSB repair and V(D)J recombination.
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
N V
NV
Boubnov
K T
KT
Hall
Z
Z
Wills
S E
SE
Lee
D M
DM
He
D M
DM
Benjamin
C R
CR
Pulaski
H
H
Band
W
W
Reeves
E A
EA
Hendrickson
D000818:Animals; D034961:Antigens, Nuclear; D016466:CHO Cells; D002459:Cell Fusion; D002460:Cell Line; D006224:Cricetinae; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004265:DNA Helicases; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000502:physiology*; D005816:Genetic Complementation Test; D006801:Humans; D000072200:Ku Autoantigen; D009154:Mutation / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011836:Radiation Tolerance / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics*
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D004247:DNA; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen