Ku, a DNA repair protein with multiple cellular functions?

The Ku protein binds to DNA ends and other types of discontinuity in double -stranded DNA. It is a tightly associated heterodimer of similar to 70 kDa and similar to 80 kDa subunits that together with the similar to 470 kDa ca talytic subunit, DNA-PKcs, form the DNA-dependent protein kinase, This enzy me is involved in repairing DNA double-strand breaks (DSBs) caused, for exa mple, by physiological oxidation reactions, V(D)J recombination, ionizing r adiation and certain chemotherapeutic drugs. The Ku-dependent repair proces s, called illegitimate recombination or nonhomologous end joining (NHEJ), a ppears to be the main DNA DSB repair mechanism in mammalian cells. Ku itsel f is probably involved in stabilizing broken DNA ends, bringing them togeth er and preparing them for ligation. Ku also recruits DNA-PKcs to the DSB, a ctivating its kinase function. Targeted disruption of the genes encoding Ku 70 and Ku80 has identified significant differences between Ku-deficient mic e and DNA-PKcs-deficient mice. Although all three gene products are clearly involved in repairing ionizing radiation-induced damage and in V(D)J recom bination, Ku-knockout mice are small, and their cells fail to proliferate i n culture and show signs of premature senescence. Recent findings have impl icated yeast Ku in telomeric structure in addition to NHEJ, Some of the phe notypes of the Ku-knockout mice may indicate a similar role for Ku at mamma lian telomeres. (C) 1999 Elsevier Science B.V. All rights reserved.