Palindrome-Mediated Translocations in Humans: A New Mechanistic Model for Gross Chromosomal Rearrangements.
Palindrome-Mediated Translocations in Humans: A New Mechanistic Model for Gross Chromosomal Rearrangements.
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DOI：
10.3389/fgene.2016.00125
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发表时间：
2016
影响因子：
3.7
通讯作者：
Kurahashi H
中科院分区：
文献类型：
--
作者：
Inagaki H;Kato T;Tsutsumi M;Ouchi Y;Ohye T;Kurahashi H
回文DNA序列广泛分布于人类基因组中，可形成二级结构。虽然二级结构的性质-单链“发夹”或双链“十字形”-已在体外进行了广泛的研究，这种不寻常的非B DNA在体内的存在仍然存在争议。在这里，我们审查回文介导的总染色体重排可能引起的非B DNA在人类。下一代测序的最新进展尚未克服回文序列分析的困难。然而，十几个回文AT丰富重复序列（PATRR）序列已被确定在人类复发性或非复发性染色体易位的断点。断裂总是发生在回文的中心。回文内的多态性分析表明，回文的对称性和长度影响的频率从头发生这些回文介导的易位，这表明参与非B DNA。事实上，使用基于质粒的模型系统的实验表明，非B DNA的形成可能是回文介导的基因组重排的关键。有证据表明，十字形DNA可能首先在细胞核内相互靠近，然后发生不规则连接，这是一种新的机制。分析人类中PATRR介导的易位将提供对许多生物体中总染色体重排的进一步理解。
Palindromic DNA sequences, which can form secondary structures, are widely distributed in the human genome. Although the nature of the secondary structure—single-stranded “hairpin” or double-stranded “cruciform”—has been extensively investigated in vitro, the existence of such unusual non-B DNA in vivo remains controversial. Here, we review palindrome-mediated gross chromosomal rearrangements possibly induced by non-B DNA in humans. Recent advances in next-generation sequencing have not yet overcome the difficulty of palindromic sequence analysis. However, a dozen palindromic AT-rich repeat (PATRR) sequences have been identified at the breakpoints of recurrent or non-recurrent chromosomal translocations in humans. The breakages always occur at the center of the palindrome. Analyses of polymorphisms within the palindromes indicate that the symmetry and length of the palindrome affect the frequency of the de novo occurrence of these palindrome-mediated translocations, suggesting the involvement of non-B DNA. Indeed, experiments using a plasmid-based model system showed that the formation of non-B DNA is likely the key to palindrome-mediated genomic rearrangements. Some evidence implies a new mechanism that cruciform DNAs may come close together first in nucleus and illegitimately joined. Analysis of PATRR-mediated translocations in humans will provide further understanding of gross chromosomal rearrangements in many organisms.