a genetic and structural study of genome rearrangements mediated by high copy repeat ty1 elements基因和结构基因重组的研究由高拷贝重复ty1元素.pdfVIP

A Genetic and Structural Study of Genome Rearrangements Mediated by High Copy Repeat Ty1 Elements Jason E. Chan1,2,3,4,5, Richard D. Kolodner2,3,4,5* 1 Bioinformatics and Systems Biology Graduate Program, University of California San Diego, La Jolla, California, United States of America, 2 Ludwig Institute for Cancer Research, University of California San Diego School of Medicine, La Jolla, California, United States of America, 3 Departments of Medicine and Cellular and Molecular Medicine, University of California San Diego School of Medicine, La Jolla, California, United States of America, 4 Moores–UCSD Cancer Center, University of California San Diego School of Medicine, La Jolla, California, United States of America, 5 Institute of Genomic Medicine, University of California San Diego School of Medicine, La Jolla, California, United States of America Abstract 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