回文序列诱导突变的机制及人类相关疾病

The mechanisms of palindrome-stimulated mutation and related human diseases

在原核和真核生物基因组中,含有回文序列的区域高度可变且稳定性差,主要原因是回文序列能形成发卡或十字形二级结构,然后通过滑动错配、单链复性以及非同源末端连接(Non-homologous end joining,NHEJ)等机制导致缺失突变或染色体易位的发生。在人类基因组中,回文序列较普遍存在于基因表达调控的重要作用元件中,它诱导的缺失和易位突变还与男性不育、地中海贫血等多种疾病的发生、发展密切相关。文章综合近几年国内外相关文献,初步阐释回文序列诱导突变的类型和可能机制,及其与人类疾病的关系,为进一步探讨回文序列在基因表达调控、基因突变及人类疾病中的作用及功能等相关研究提供参考。

In prokaryotic and eukaryotic genomes, the palindrome regions are highly variable and instable. The reason for this instability is that palindrome can form a hairpin or cruciform structure, which can result in deletions or chromosomal translocations by certain mechanisms, such as slipped mispairing, single-strand annealing and non-homologous end joining. In human genomes, palindromes commonly exist in the essential elements which can regulate the expressions of different genes, and the mutations stimulated by palindromes are also closely associated with the occurrences and progressions of certain human diseases such as male infertility and thalassemia. Based on recent studies, we briefly summarize the types of mutations caused by palindromes and their possible mechanisms, as well as the related human diseases. This review would provide some information for the following researches about the roles and functions of palindromes in gene expression, regulation, mutation and related human diseases.