* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Slide 1
Extrachromosomal DNA wikipedia , lookup
Zinc finger nuclease wikipedia , lookup
Nucleic acid analogue wikipedia , lookup
Nucleic acid double helix wikipedia , lookup
Holliday junction wikipedia , lookup
Oncogenomics wikipedia , lookup
Genome (book) wikipedia , lookup
History of genetic engineering wikipedia , lookup
Primary transcript wikipedia , lookup
Designer baby wikipedia , lookup
Microevolution wikipedia , lookup
No-SCAR (Scarless Cas9 Assisted Recombineering) Genome Editing wikipedia , lookup
Vectors in gene therapy wikipedia , lookup
Cre-Lox recombination wikipedia , lookup
Deoxyribozyme wikipedia , lookup
Point mutation wikipedia , lookup
DNA nanotechnology wikipedia , lookup
Sequence alignment wikipedia , lookup
Nucleic acid tertiary structure wikipedia , lookup
Site-specific recombinase technology wikipedia , lookup
Telomerase reverse transcriptase wikipedia , lookup
Microsatellite wikipedia , lookup
Non-coding DNA wikipedia , lookup
Neocentromere wikipedia , lookup
Therapeutic gene modulation wikipedia , lookup
Metagenomics wikipedia , lookup
Human genome wikipedia , lookup
Helitron (biology) wikipedia , lookup
Human–animal hybrid wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
In the name of GOD Zeinab Mokhtari 1 12-Oct-2011 Arizona University Danzhou Yang 2 Telomeres are specialized DNA sequences that cap the ends of linear chromosomes and provide protection against gene erosion at cell divisions, chromosomal non-homologous end-joinings and nuclease attacks. aging cancer genetic stability a single-stranded 30-overhang of 100–200 bases 3 11_chemsocrev_telomere_review apoptosis telomeres of cancer cells due to the activation of a reverse transcriptase, telomerase, that extends the telomeric sequence at the chromosome ends 4 malignant phenotype G-quadruplex DNA secondary structures that consist of stacked G-tetrad planes connected by a network of Hoogsteen hydrogen bonds and stabilized by monovalent cations. 5 11_chemsocrev_telomere_review inhibits the activity of telomerase K+ structure is considered to be biologically more relevant due to the higher intracellular concentration of K+ structure-based rational drug design 6 four G-tract human telomeric sequence 5’-GGG(TTAGGG)3 Minimume 7 1993: 22-nt human telomeric sequence, in the presence of Na+ 8 2002: a crystal structure of the parallel-stranded G-quadruplex, 22-nt human telomeric sequence, in the presence of K+. 9 predominant conformations formed in human telomeric sequences in K+ solution HYBRID 1 HYBRID 2 HYBRID 1 & 2 diff.s : Mixed par (3) & antipar(1- 3rd)Loop arrangements Mixed par (3) & antipar(1- 2nd) Strands orientations Side-lateral-lateral lateral-lateral-side G-tetrad arrangements 5 syn Gs 5 syn Gs Capping structures Top end cap: A triple 10 Bottom end cap: A:T base pair Bottom end cap: T:A:T triple sequences with a 3’-flanking wtTel27 wtTel26 wtTel25b wtTel24b wtTel25a sequences with no 3’-flanking segment wtTel23 wtTel24 dynamic equilibrium The 3’-flanking-T(T25) is necessary for the formation of the T:A:T triple capping structure, which selectively stabilizes the hybrid-2 type telomeric G-quadruplex. Addition of K+ readily converts the Na-form conformation to the K-form hybrid-type structures. 12 Hybrid-type structures are the predominant conformations for wtTel26 and Tel26 in K solution, even in the co-presence of a high concentration of Na 13 Thanks