Ku Autoantigen: A Multifunctional DNA-binding Protein

Crit Rev Biochem Mol Biol. 2000;35(1):1-33. doi: 10.1080/10409230091169177.

Abstract

Ku is a heterodimeric protein composed of approximately 70- and approximately 80-kDa subunits (Ku70 and Ku80) originally identified as an autoantigen recognized by the sera of patients with autoimmune diseases. Ku has high binding affinity for DNA ends and that is why originally it was known as a DNA end binding protein, but now it is known to also bind the DNA structure at nicks, gaps, hairpins, as well as the ends of telomeres. It has been reported also to bind with sequence specificity to DNA and with weak affinity to RNA. Ku is an abundant nuclear protein and is present in vertebrates, insects, yeast, and worms. Ku contains ssDNA-dependent ATPase and ATP-dependent DNA helicase activities. It is the regulatory subunit of the DNA-dependent protein kinase that phosphorylates many proteins, including SV-40 large T antigen, p53, RNA-polymerase II, RP-A, topoisomerases, hsp90, and many transcription factors such as c-Jun, c-Fos, oct-1, sp-1, c-Myc, TFIID, and many more. It seems to be a multifunctional protein that has been implicated to be involved directly or indirectly in many important cellular metabolic processes such as DNA double-strand break repair, V(D)J recombination of immunoglobulins and T-cell receptor genes, immunoglobulin isotype switching, DNA replication, transcription regulation, regulation of heat shock-induced responses, regulation of the precise structure of telomeric termini, and it also plays a novel role in G2 and M phases of the cell cycle. The mechanism underlying the regulation of all the diverse functions of Ku is still obscure.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphatases
  • Antigens, Nuclear*
  • Autoantigens / metabolism*
  • Cell Cycle Proteins
  • DNA Helicases
  • DNA Repair
  • DNA-Activated Protein Kinase
  • DNA-Binding Proteins / metabolism*
  • Immunoglobulin Class Switching
  • Ku Autoantigen
  • Nuclear Proteins / metabolism*
  • Protein-Serine-Threonine Kinases
  • Recombination, Genetic
  • Saccharomyces cerevisiae Proteins*
  • Transcription, Genetic

Substances

  • Antigens, Nuclear
  • Autoantigens
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Saccharomyces cerevisiae Proteins
  • high affinity DNA-binding factor, S cerevisiae
  • DNA-Activated Protein Kinase
  • Protein-Serine-Threonine Kinases
  • Adenosine Triphosphatases
  • single stranded DNA dependent ATPase
  • DNA Helicases
  • XRCC5 protein, human
  • Xrcc6 protein, human
  • Ku Autoantigen