Deleted in breast cancer 1 (DBC1) deficiency results in apoptosis of breast cancer cells through impaired responses to UV-induced DNA damage.
DBC1 (deleted in breast cancer 1) participates in the regulation of cell survival and death in response to various stimuli. In particular, DBC1 promotes cell death upon DNA damage through inhibition of SIRT1 deacetylase. However, the SIRT1-independent functions of DBC1 in the regulation of DNA damage response are less well understood. Therefore, we analyzed the DNA damage response in Hs578T breast cancer cell line in which the DBC1-SIRT1 interaction is barely detectable. DBC1-siRNA transfected cells showed a failure in the DNA damage checkpoint and the accumulation of genomic damage following UV irradiation. In addition, DBC1-deficient cells exhibited less JNK activation. Finally, the interruptions of signaling in DBC1-depleted cells contributed to cell death in response to UV irradiation. Overall, these data suggest that DBC1 is essential for a fully efficient and effective response to UV irradiation. Therefore, DBC1 plays a critical role in maintaining genomic stability and cellular integrity following UV-induced genotoxic stress.
Department of Pharmacology, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
Wootae
W
Kim
Ja-Eun
JE
Kim
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology* / Q000532:radiotherapy; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D002843:Chromatin / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects*; D005260:Female; D042822:Genomic Instability / Q000528:radiation effects; D006801:Humans; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays
D048868:Adaptor Proteins, Signal Transducing; C527450:CCAR2 protein, human; D002843:Chromatin; C447939:SIRT1 protein, human; D056564:Sirtuin 1