DNA adducts of antitumor cisplatin preclude telomeric sequences from forming G quadruplexes
Jazyk angličtina Země Německo Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
55005613
Howard Hughes Medical Institute - United States
- MeSH
- adukty DNA účinky léků genetika metabolismus MeSH
- biokatalýza MeSH
- cirkulární dichroismus MeSH
- cisplatina chemie farmakologie MeSH
- denaturace nukleových kyselin MeSH
- elektroforéza v polyakrylamidovém gelu MeSH
- G-kvadruplexy účinky léků MeSH
- lidé MeSH
- protinádorové látky chemie farmakologie MeSH
- sekvence nukleotidů MeSH
- spektrofotometrie ultrafialová MeSH
- techniky amplifikace nukleových kyselin MeSH
- telomerasa antagonisté a inhibitory metabolismus MeSH
- telomery chemie genetika MeSH
- tranzitní teplota MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adukty DNA MeSH
- cisplatina MeSH
- protinádorové látky MeSH
- telomerasa MeSH
- transplatin MeSH Prohlížeč
We studied the effect of antitumor cisplatin and inefficient transplatin on the structure and stability of G quadruplexes formed by the model human telomere sequence 5'-GGG(TTAGGG)(3)-3' using circular dichroism, UV-monitored thermal denaturation, and gel electrophoresis. In addition, to investigate whether there is a connection between the ability of cisplatin or transplatin to affect telomerase activity and stability of G quadruplexes, we also used a modified telomere repeat amplification protocol assay that uses an oligonucleotide substrate for telomerase elongation susceptible to forming a G quadruplex. The results indicate that cisplatin is more efficient than transplatin in disturbing the quadruplex structure, thereby precluding telomeric sequences from forming quadruplexes. On the other hand, the results of this work also demonstrate that in absence of free platinum complex, DNA adducts of antitumor cisplatin inhibit telomerase catalysis, so the mechanism underlying this inhibition does not involve formation of the G quadruplexes which are not elongated by telomerase.
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