Evidence for a role of vertebrate Rad52 in the repair of topoisomerase II-mediated DNA damage.
DNA topoisomerase II (Top2) inhibitors are useful as anticancer agents, mostly by virtue of their ability to induce DNA double-strand breaks (DSBs). These DSBs are repaired almost exclusively by Rad52-dependent homologous recombination (HR) in yeast. However, we have recently shown that in vertebrate cells such lesions are primarily repaired by nonhomologous end-joining, but not HR. This finding, taken together with previous observations that disruption of RAD52 does not severely affect HR in vertebrate cells, makes it highly unlikely that Rad52 contributes to the repair of Top2-mediated DNA damage. However, in this paper we show that chicken cells lacking Rad52 do exhibit increased sensitivity to the Top2 inhibitor VP-16. Remarkably, the level of hypersensitivity of RAD52-null cells was comparable to that of RAD54-null cells, albeit only at high doses. Our data thus provide the first demonstration of a major repair defect associated with loss of Rad52 in vertebrate cells.
Adachi
Noritaka
N
Kihara Institute for Biological Research, Graduate School of Integrated Science, Yokohama City University, Yokohama, Japan. nadachi@yokohama-cu.ac.jp
Iiizumi
Susumu
S
Koyama
Hideki
H
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002645:Chickens; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D054659:Diketopiperazines; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D009154:Mutation; D010879:Piperazines / Q000494:pharmacology; D051721:Rad52 DNA Repair and Recombination Protein; D011995:Recombination, Genetic; D059005:Topoisomerase II Inhibitors
D004268:DNA-Binding Proteins; D054659:Diketopiperazines; D004791:Enzyme Inhibitors; D010879:Piperazines; D051721:Rad52 DNA Repair and Recombination Protein; D059005:Topoisomerase II Inhibitors; C070899:4,4'-(1,2-dimethyl-1,2-ethanediyl)bis-2,6-piperazinedione; D005047:Etoposide; D004250:DNA Topoisomerases, Type II