Stability of intrastrand hairpin structures formed by the CAG/CTG class of DNA triplet repeats associated with neurological diseases
Stability of intrastrand hairpin structures formed by the CAG/CTG class of DNA triplet repeats associated with neurological diseases
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DOI：
10.1093/nar/24.11.1992
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发表时间：
1996-06-01
影响因子：
14.9
通讯作者：
Goodman, MF
中科院分区：
文献类型：
--
作者：
Petruska, J;Arnheim, N;Goodman, MF
DNA中三核苷酸重复序列的扩增是与人类疾病相关的突变的新来源，其可能由含有此类重复序列的引物或模板链的发夹折叠引发的DNA复制滑移引起。为了评价通过重复DNA碱基三联体进行的单链折叠的稳定性，使用（CAG）（10）、（CTG）（11）、（CTG）（12）、（CTG）（13）、（CTG）（14）、（CTG）（15）、（CTG）（16）、（CTG）（17）、（CTG）（18）、（CTG）（19）、（19）在法定和生理盐浓度下测定（GAC）（10）和（GTC）（10）链，并在每种情况下测量熔融温度和焓变。与具有三倍重复的链（CAG）（30）和（CTG）（30）进行比较。CAG/CTG类三联体重复序列的链内折叠稳定性较好，相对于与疾病无关的GAC/GTC类，10个重复序列的折叠稳定性顺序为CTG> GAC> CAG> GTC。由30个重复的CTG或CAG形成的折叠没有更高的解链温度并且自由能仅比由10个重复形成的折叠稳定40%，这一发现表明，具有较高重复数的三联体扩增可能是由于形成了具有相似稳定性的更多折叠结构，而不是更少但更长的稳定性更高的折叠。
Expansions of trinucleotide repeats in DNA, a novel source of mutations associated with human disease, may arise by DNA replication slippage initiated by hairpin folding of primer or template strands containing such repeats, To evaluate the stability of single-strand folding by repeating triplets of DNA bases, thermal melting profiles of (CAG)(10), (CTG)(10), (GAC)(10) and (GTC)(10) strands are determined at law and physiological salt concentrations, and measurements of melting temperature and enthalpy change are made in each case, Comparisons are made to strands with three times as many repeats, (CAG)(30) and (CTG(30). Evidence is presented for stable intrastrand folding by the CAG/CTG class of triplet repeats, Relative to the GAC/GTC class not associated with disease, the order of folding stability is found to be CTG > GAC approximate to CAG > GTC for 10 repeats, Surprisingly, the folds formed by 30 repeats of CTG or CAG have no higher melting temperature and are only 40% more stable in free energy than those formed by 10 repeats, This finding suggests that triplet expansions with higher repeat number may result from the formation of more folded structures with similar stability rather than fewer but longer folds of greater stability.