tailieunhanh - Báo cáo khoa học: Human telomeric G-quadruplex: structures of DNA and RNA sequences

The innate immune response of insects includes induced expression of genes encoding a variety of antimicrobial peptides. The signaling pathways that stimulate this gene expression have been well characterized by genetic analy-sis in Drosophila melanogaster, but are not well understood in most other insect species. | ỊFEBS Journal MINIREVIEW Human telomeric G-quadruplex structures of DNA and RNA sequences Anh Tuân Phan Schoolof Physical MathematicalSciences Nanyang TechnologicalUniversity Singapore Keywords DNA G-quadruplex G-quadruplex structure G-quadruplex topology G-tetrad G-tetrad core grooves in G-quadruplexes human telomere loops in G-quadruplexes RNA Correspondence A. T. Phan Division of Physics Applied Physics Schoolof Physical Mathematical Sciences Nanyang TechnologicalUniversity Singapore 637371 Fax 65 6795 7981 Tel 65 6514 1915 E-mail phantuan@ Received 25 June 2009 revised 14 September 2009 accepted 6 October 2009 doi Telomeres play an important role in cellular aging and cancer. Human telomeric DNA and RNA G-rich sequences are capable of forming a four-stranded structure known as the G-quadruplex. Such a structure might be important for telomere biology and a good target for drug design. This minireview describes the structural diversity or conservation of DNA and RNA human telomeric G-quadruplexes discusses structural views on targeting these G-quadruplexes and presents some future challenges for structural studies. Introduction Human telomeric DNA contains thousands of tandem repeats of the G-rich GGGTTA n sequence 1 with a 3 -end overhang of 100-200 nucleotides 2 . Telomeres can be transcribed by DNA-dependent RNA polymerase II and telomeric-repeat-containing RNA molecules ranging from 100 to 9000 nucleotides have been detected in nuclear fractions 3-5 . Under physiological ionic conditions human telomeric DNA and RNA G-rich sequences are capable of forming a four-stranded helical structure known as the G-quadruplex 6-14 based on the stacking of multiple G G G G tetrads or G-tetrads 15 Fig. 1A . Such a structure might be important for telomere biology 5-14 16-19 and a good target for drug design 5-14 19-21 . G-quadruplex structures formed by various G-rich sequences have been reviewed previously 6-14 . This minireview