Bioinformatics and Systems Biology Graduate Program, University of California San Diego, La Jolla, California, United States of America.
PLoS Genet. 2011 May;7(5):e1002089. doi: 10.1371/journal.pgen.1002089. Epub 2011 May 26.
Ty elements are high copy number, dispersed repeated sequences in the Saccharomyces cerevisiae genome known to mediate gross chromosomal rearrangements (GCRs). Here we found that introduction of Ty912, a previously identified Ty1 element, onto the non-essential terminal region of the left arm of chromosome V led to a 380-fold increase in the rate of accumulating GCRs in a wild-type strain. A survey of 48 different mutations identified those that either increased or decreased the rate of Ty-mediated GCRs and demonstrated that suppression of Ty-mediated GCRs differs from that of both low copy repeat sequence- and single copy sequence-mediated GCRs. The majority of the Ty912-mediated GCRs observed were monocentric nonreciprocal translocations mediated by RAD52-dependent homologous recombination (HR) between Ty912 and a Ty element on another chromosome arm. The remaining Ty912-mediated GCRs appeared to involve Ty912-mediated formation of unstable dicentric translocation chromosomes that were resolved by one or more Ty-mediated breakage-fusion-bridge cycles. Overall, the results demonstrate that the Ty912-mediated GCR assay is an excellent model for understanding mechanisms and pathways that suppress genome rearrangements mediated by high copy number repeat sequences, as well as the mechanisms by which such rearrangements occur.
Ty 元件是高度重复的序列，分散在酿酒酵母基因组中，已知它们介导染色体的大规模重排（GCRs）。在这里，我们发现将先前鉴定的 Ty1 元件 Ty912 引入染色体 V 的左臂非必需末端区域，会导致野生型菌株中 GCRs 的积累率增加 380 倍。对 48 种不同突变的调查确定了那些增加或降低 Ty 介导 GCRs 速率的突变，并表明 Ty 介导 GCRs 的抑制与低拷贝重复序列和单拷贝序列介导的 GCRs 的抑制不同。观察到的大多数 Ty912 介导的 GCRs 是由 RAD52 依赖性同源重组（HR）介导的单中心非相互易位，该重组发生在 Ty912 与另一条染色体臂上的 Ty 元件之间。剩下的 Ty912 介导的 GCRs 似乎涉及 Ty912 介导的不稳定双中心易位染色体的形成，这些染色体通过一个或多个 Ty 介导的断裂-融合-桥循环来解决。总的来说，这些结果表明，Ty912 介导的 GCR 测定是一个很好的模型，可以帮助我们理解抑制由高拷贝重复序列介导的基因组重排的机制和途径，以及这些重排发生的机制。
