TETRAPLEX FOLDING OF TELOMERE SEQUENCES AND THE INCLUSION OF ADENINE BASES

被引:55
作者
MURCHIE, AIH [1 ]
LILLEY, DMJ [1 ]
机构
[1] UNIV DUNDEE, DEPT BIOCHEM, CRC, NUCLE ACID STRUCT RES GRP, DUNDEE DD1 4HN, SCOTLAND
关键词
DNA STRUCTURE; GUANINE QUARTET; TELOMERE; TETRAD;
D O I
10.1002/j.1460-2075.1994.tb06344.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Telomeres are required for eukaryotic chromosome stability. They consist of regularly repeating guanine-rich sequences, with a single-stranded 3' terminus. Such sequences have been demonstrated to have the propensity to adopt four-stranded structures based on a tetrad of guanine bases. The formation of an intramolecular foldback tetraplex is associated,vith markedly increased mobility in polyacrylamide. Most telomeric sequences are based either on a repeat of d(T(n)GGGG) or d(T(n)AGGG) sequences. We have used a combination 7-deazaguanine or 7-deaza-adenine substitution, chemical modification and gel electrophoresis to address the following aspects of intramolecular tetraplex formation. (i) Intramolecular tetraplex formation by d(TTTTGGGG)(4) sequences is prevented by very low levels of 7-deazaguanine substitution. This confirms the important role of guanine N-7 in the formation of the tetraplex. (ii) The sequences d(TTAGGG)(4) and d(TTTTAGGG)(4) fold into tetraplexes. By contrast, the electrophoretic behaviour of d(TTTTGGGA)(4), d(TTTTAGAG)(4) and d(TTTTGAGA)(4) does not indicate formation of stable intramolecular tetraplexes under available conditions. (iii) Selective 7-deazaguanine and 7-deaza-adenine substitutions in d(TTTTAGGG)(4) give results consistent with tetraplex folding by the formation of three G(4) tetrads, with the adenine bases formally part of the single-stranded loops, where they probably interact with thymine bases. These results demonstrate that eukaryotic cells appear to have selected just those sequences that can adopt the tetraplex conformation for their telomeres, while those that cannot have been avoided. This suggests that the conformation may be significant in the function of the telomere, such as attachment to nuclear structures.
引用
收藏
页码:993 / 1001
页数:9
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