tailieunhanh - Báo cáo khoa học: Platination of telomeric sequences and nuclease hypersensitive elements of human c-myc and PDGF-A promoters and their ability to form G-quadruplexes Viktor Viglasky

Naturally occurring G-rich DNA sequences that are able to form G-quad-ruplex structures appear as potential targets for anti-cancer chemotherapy, and therefore play an important role in cellular processes, such as cell aging, death and carcinogenesis. | ỊFEBS Journal Platination of telomeric sequences and nuclease hypersensitive elements of human c-myc and PDGF-A promoters and their ability to form G-quadruplexes Viktor Viglasky Department of Biochemistry Faculty of Sciences Institute of Chemistry P. J. Safarik University Kosice Slovakia Keywords cisplatin c-myc G-quadruplex PDGF-A promoter telomeric sequences Correspondence V. Viglasky Department of Biochemistry Faculty of Sciences Institute of Chemistry Safarik University Moyzesova 11 04011 Kosice Slovakia Fax 421 55 622 21 24 Tel 421 55 234 12 62 E-mail Received 30 August 2008 revised 5 November 2008 accepted 7 November 2008 doi Naturally occurring G-rich DNA sequences that are able to form G-quad-ruplex structures appear as potential targets for anti-cancer chemotherapy and therefore play an important role in cellular processes such as cell aging death and carcinogenesis. The telomeric regions of DNA and nuclease hypersensitive elements of human c-myc and PDGF-A promoters represent a very appealing target for cisplatin and may interfere with normal DNA function. Platinum complexes bind covalently to nucleobases and especially to the N7 atom of guanines and the four guanines of a G-quar-tet have their N7 atoms involved in hydrogen bonding. Therefore within a G-quadruplex structure only the guanines out of the stack of G-quartets should react with electrophilic species such as platinum II complexes. Platinum complexes have significant influence on the formation of G-quad-ruplexes. Results obtained by CD spectroscopy and temperature gradientgel electrophoresis clearly demonstrate that DNA platination significantly affects G-quadruplex folding for telomeric sequences the abundance of un misfolded DNAs compared to the G-quadruplex is proportional to the platinum concentration. G-rich regions appear in several locations in the human genome including at the ends of linear chrom-omes the immunoglobin switch .