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Báo cáo khoa học: Making sense of G-quadruplex and i-motif functions in oncogene promoters

The presence and biological importance of DNA secondary structures in eukaryotic promoters are becoming increasingly recognized among chemists and biologists as bioinformatics in vitro and in vivo evidence for these structures in the c-Myc, c-Kit, KRAS, PDGF-A, hTERT, Rb, RET and Hif-1apromoters accumulates. | ỊFEBS Journal MINIREVIEW Making sense of G-quadruplex and i-motif functions in oncogene promoters Tracy A. Brooks1 2 3 Samantha Kendrick3 and Laurence Hurley1 2 3 1 University of Arizona College of Pharmacy Tucson USA 2 University of Arizona BIO5 Institute Tucson USA 3 University of Arizona Arizona Cancer Center Tucson USA Keywords Bcl-2 c-Myc DNA secondary structures G-quadruplex gene expression i-motif NM23-H2 nucleolin promoter supercoiling Correspondence L. Hurley University of Arizona College of Pharmacy Tucson AZ 85721 USA Fax 1 520 626 0035 Tel 1 520 626 5622 E-mail hurley@pharmacy.arizona.edu The presence and biological importance of DNA secondary structures in eukaryotic promoters are becoming increasingly recognized among chemists and biologists as bioinformatics in vitro and in vivo evidence for these structures in the c-Myc c-Kit KRAS PDGF-A hTERT Rb RET and Hif-1a promoters accumulates. Nevertheless the evidence remains largely circumstantial. This minireview differs from previous ones in that here we examine the diversity of G-quadruplex and i-motif structures in promoter elements and attempt to categorize the different types of arrangements in which they are found. For the c-Myc G-quadruplex and Bcl-2 i-motif we summarize recent biological and structural studies. Received 23 February 2010 revised 29 April 2010 accepted 28 May 2010 doi 10.1111 j.1742-4658.2010.07759.x Introduction Although recent reviews on G-quadruplexes in telomeres have been published 1-3 in this minireview we focus on the increasingly observed complexity of G-quadruplex G-rich strand and i-motif C-rich strand folding patterns and structures in the promoter regions of oncogenes. Accompanying minireviews in this issue discuss other aspects of the biology of G-quadru-plexes 4 5 . In previous bioinformatics searches 6 7 relatively simple algorithms have been used to examine promoter regions for G-quadruplexes but it is likely that more-defined subcategory algorithm searches might .