期刊
BIOCHEMISTRY
卷 57, 期 51, 页码 6946-6955出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.biochem.8b00957
关键词
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资金
- National Institutes of HEalth [1R01CA236350]
- National Science Foundation (NSF) [CHE-1415883]
- NSF [CHE-1609514]
- JSPS [23310158, 26282214, 21655060, 16K13094]
- JSPS Predoctoral Fellowships for Young Scientists
- Grants-in-Aid for Scientific Research [16K13094, 21655060, 26282214] Funding Source: KAKEN
G-Quadruplexes formed in the 3' telomere overhang (similar to 200 nucleotides) have been shown to regulate biological functions of human telomeres. The mechanism governing the population pattern of multiple telomeric G-quadruplexes is yet to be elucidated inside the telomeric overhang in a time window shorter than thermodynamic equilibrium. Using a single-molecule force ramping assay, we quantified G-quadruplex populations in telomere overhangs over a full physiological range of 99-291 nucleotides. We found that G-quadruplexes randomly form in these overhangs within seconds, which leads to a population governed by a kinetic, rather than a thermodynamic, folding pattern. The kinetic folding gives rise to vacant G-tracts between G-quadruplexes. By targeting these vacant G-tracts using complementary DNA fragments, we demonstrated that binding to the telomeric G-quadruplexes becomes more efficient and specific for telomestatin derivatives.
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