regulation and role of arabidopsis cul4-ddb1a-ddb2 in maintaining genome integrity upon uv stress监管和拟南芥cul4-ddb1a-ddb2维持基因组完整性的作用在紫外线的压力.pdfVIP

Regulation and Role of Arabidopsis CUL4-DDB1A-DDB2 in Maintaining Genome Integrity upon UV Stress Jean Molinier, Esther Lechner, Eva Dumbliauskas, Pascal Genschik* ´ ´ ´ Institut de Biologie Moleculaire des Plantes du CNRS (UPR2357), conventionne avec l’Universite Louis Pasteur, Strasbourg, France Abstract Plants use the energy in sunlight for photosynthesis, but as a consequence are exposed to the toxic effect of UV radiation especially on DNA. The UV-induced lesions on DNA affect both transcription and replication and can also have mutagenic consequences. Here we investigated the regulation and the function of the recently described CUL4-DDB1-DDB2 E3 ligase in the maintenance of genome integrity upon UV-stress using the model plant Arabidopsis. Physiological, biochemical, and genetic evidences indicate that this protein complex is involved in global genome repair (GGR) of UV-induced DNA lesions. Moreover, we provide evidences for crosstalks between GGR, the plant-specific photo reactivation pathway and the RAD1- RAD10 endonucleases upon UV exposure. Finally, we report that DDB2 degradation upon UV stress depends not only on CUL4, but also on the checkpoint protein kinase Ataxia telangiectasia and Rad3-related (ATR). Interestingly, we found that DDB1A shuttles from the cytoplasm to the nucleus in an ATR-dependent manner, highlighting an upstream level of control and a novel mechanism of regulation of this E3 ligase. Citation: Molinier J, Lechner E, Dumbliauskas E, Genschik P (2008) Regulation and Role of Arabidopsis CUL4-DDB1A-DDB2 in Maintaining Genome Integrity upon UV Stress. PLoS Genet 4(6): e1000093. doi:10.1371/journal.pgen.1000093 Editor: Gregory P. Copenhaver, The University of North Carolina at Chapel Hill, United States of America Received March 13, 2008; Accepted May 12, 2008; Pub