The ionizing radiation-induced replication protein A phosphorylation response differs between ataxia telangiectasia and normal human cells.

AUTOR(ES)

Liu, V F

RESUMO

Replication protein A (RPA), the trimeric single-stranded DNA-binding protein complex of eukaryotic cells, is important to DNA replication and repair. Phosphorylation of the p34 subunit of RPA is modulated by the cell cycle, occurring during S and G2 but not during G1. The function of phosphorylated p34 remains unknown. We show that RPA p34 phosphorylation is significantly induced by ionizing radiation. The phosphorylated form, p36, is similar if not identical to the phosphorylated S/G2 form. gamma-Irradiation-induced phosphorylation occurs without new protein synthesis and in cells in G1. Mutation of cdc2-type protein kinase phosphorylation sites in p34 eliminates the ionizing radiation response. The gamma-irradiation-induced phosphorylation of RPA p34 is delayed in cells from ataxia telangiectasia, a human inherited disease conferring DNA repair defects and early-onset tumorigenesis. UV-induced phosphorylation of RPA p34 occurs less rapidly than gamma-irradiation-induced phosphorylation but is kinetically similar between ataxia telangiectasia and normal cells. This is the first time that modification of a repair protein, RPA, has been linked with a DNA damage response and suggests that phosphorylation may play a role in regulating DNA repair pathways.

Documentos Relacionados

• The role of inhibitory phosphorylation of CDC2 following DNA replication block and radiation-induced damage in human cells.
• Base substitutions, frameshifts, and small deletions constitute ionizing radiation-induced point mutations in mammalian cells.
• Replication of Radiation-Induced Murine Leukemia Virus in Normal and Transformed Mouse Cells
• Effect of ionizing radiation on DNA synthesis in ataxia telangiectasia cells.
• Atm and Bax cooperate in ionizing radiation-induced apoptosis in the central nervous system