distinct functions for the drosophila pirna pathway in genome maintenance and telomere protection不同功能基因组的果蝇pirna途径维护和端粒的保护.pdfVIP

Distinct Functions for the Drosophila piRNA Pathway in Genome Maintenance and Telomere Protection 1 2 3 1 Jaspreet S. Khurana , Jia Xu , Zhiping Weng , William E. Theurkauf * 1 Program in Cell and Developmental Dynamics and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America, 2 Department of Biomedical Engineering, Boston University, Boston, Massachusetts, United States of America, 3 Program in Bioinformatics and Integrative Biology and Department in Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America Abstract Transposons and other selfish DNA elements can be found in all phyla, and mobilization of these elements can compromise genome integrity. The piRNA (PIWI-interacting RNA) pathway silences transposons in the germline, but it is unclear if this pathway has additional functions during development. Here we show that mutations in the Drosophila piRNA pathway genes, armi, aub, ago3, and rhi, lead to extensive fragmentation of the zygotic genome during the cleavage stage of embryonic divisions. Additionally, aub and armi show defects in telomere resolution during meiosis and the cleavage divisions; and mutations in lig-IV, which disrupt non-homologous end joining, suppress these fusions. By contrast, lig-IV mutations enhance chromosome fragmentation. Chromatin immunoprecipitation studies show that aub and armi mutations disrupt telomere binding of HOAP, which is a component of the telomere protection complex, and reduce expression of a subpopulation of 19- to 22-nt telomere-specific piRNAs. Mutations in rhi and ago3, by