Sperm-specific mechanism that induces the gross chromosomal rearrangements

总体染色体重排（gcr）通常是由两个DNA断裂区域之间的非法修复产生的，这些区域的核苷酸序列可能采用非b DNA结构。我们之前建立了一个基于质粒的模型系统，概括了人类中回文介导的反复易位，并证明了十字形DNA是重排所必需的。在这项研究中，我们发现两个连续的反应导致了十字形结构的分裂：gen1介导的分裂在十字形的四向交界处对角线分裂，以及artemis介导的随后形成的发夹末端的开放。同源重组中的Holliday连接分解和抗原受体基因重排中的编码连接形成这两种通常独立完成重要功能的内在途径，协同作用于不寻常的DNA构象，并导致人类复发性GCRs。

Gross chromosomal rearrangements(GCRs) are often generated by illegitimate repair between two DNA breakages at regions with nucleotide sequences that potentially adopt a non-B DNA structure. We previously established a plasmid-based model system that recapitulates palindrome-mediated recurrent translocations in humans, and demonstrated that cruciform DNA is required for the rearrangements. In this study, we show that two sequential reactions that cleave the cruciform structures induce the translocation : GEN1-mediated resolution that cleaves diagonally at the four-way junction of the cruciform, and Artemis-mediated opening of the subsequently formed hairpin ends. These two intrinsic pathways that normally fulfill vital functions independently, Holliday junction resolution in homologous recombination and coding joint formation in rearrangement of antigen-receptor genes, act upon the unusual DNA conformation in concert and lead to these recurrent GCRs in humans.