[DNA-dependent protein kinase (DNA-PK), a key enzyme in the re-ligation of double-stranded DNA breaks].
Repair pathways of DNA are now better defined, and some important findings have been discovered in the last few years. DNA non-homologous end-joining (NEHJ) is a crucial process in the repair of radiation-induced double-strand breaks (DSBs). NHEJ implies at least three steps: the DNA free-ends must get closer, preparation of the free-ends by exonucleases and then a transient hybridisation in a region of DNA with weak homology. DNA-dependent protein kinase (DNA-PK) is the key enzyme in this process. DNA-PK is a nuclear serine/threonine kinase that comprises three components: a catlytic subunit (DNA-PKCS) and two regulatory subunits, DNA-binding proteins, Ku80 and Ku70. The severe combined immunodeficient (scid) mice are deficient in DNA-PKCS: this protein is involved both in DNA repair and in the V(D)J recombination of immunoglobulin and T-cell receptor genes. It is a protein-kinase of the P13-kinase family and which can phosphorylates Ku proteins, p53 and probably some other proteins still unknown. DNA-PK is an important actor of DSBs repair (induced by ionising radiations or by drugs like etoposide), but obviously it is not the only mechanism existing in the cell for this function. Some others, like homologous recombination, seem also to have a great importance for cell survival.
Hennequin
C
C
Radiothérapie-oncologie, hôpital Saint-Louis, Paris, France.
Giocanti
N
N
Averbeck
D
D
Favaudon
V
V
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D019281:Dimerization; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009687:Nuclear Proteins; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D000077191:Wortmannin; D014983:Xeroderma Pigmentosum / Q000473:pathology
D000730:Androstadienes; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D004247:DNA; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; D000077191:Wortmannin