论文信息 - Drug Design for KU86 in DNA Break Repair System

Drug Design for KU86 in DNA Break Repair System

XRCC4 was well known as the downstream of KU86DNA complex. They both play an important role in the DNA double-strain breaks (DSBs) repair system subpathway, nonhomologous end joining (NHEJ).In this study, The protocol of docking analysis was applied to find the specific compounds, which had highest affinities to KU86 from our TCM database. The docking results were analyzed to point out potent compounds. Xanthone-9, xanthone-11, 12, and Cycloheterophyllin were suggested as leading compounds for drug design by hydrogen bonds forming on Arg403 in Ku70 and Arg400 in Ku80 Then, xanthone-11 was selected to the protocol of de novo evolution. The diversities of xanthone-11 had 10 kinds of the result of de novo evolution. We suggested that the diversities could be the potent compounds of inhibitors for KU86. KeywordsKU86; traditional Chinese medicine (TCM); DNA double-strand breaks (DSBs)

[1] F. Alt,et al. Unrepaired DNA Breaks in p53-Deficient Cells Lead to Oncogenic Gene Amplification Subsequent to Translocations , 2002, Cell.

[2] F. Alt,et al. DNA double strand break repair and chromosomal translocation: Lessons from animal models , 2001, Oncogene.

[3] K. Valerie,et al. Regulation and mechanisms of mammalian double-strand break repair , 2003, Oncogene.

[4] F. Alt,et al. Increased ionizing radiation sensitivity and genomic instability in the absence of histone H2AX , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[5] S. Kuhfittig-Kulle,et al. Pathways of DNA double-strand break repair and their impact on the prevention and formation of chromosomal aberrations , 2004, Cytogenetic and Genome Research.

[6] M. Hande,et al. DNA-PKcs is critical for telomere capping , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[7] Thomas Ried,et al. DNA repair protein Ku80 suppresses chromosomal aberrations and malignant transformation , 2000, Nature.

[8] F. Alt,et al. Interplay of p53 and DNA-repair protein XRCC4 in tumorigenesis, genomic stability and development , 2000, Nature.

[9] J. Nickoloff,et al. Regulation of DNA double-strand break repair pathway choice , 2008, Cell Research.