Forward genetic screen of human transposase genomic rearrangements

BMC Genomics

Methodology Article

Nicholas D. Socci¹  Richard Koche²  Scott A. Armstrong³  Luca Pinello⁴  Daniel E. Bauer⁴  Mithat Gonen⁵  Camila M. Villasante⁶  Anton G. Henssen⁶  Eileen Jiang⁶  Alex Kentsis⁷  Zhiping Weng⁸  Jiali Zhuang⁸ 

[1] Bioinformatics Core, Memorial Sloan Kettering Cancer Center, New York, NY, USA;Cancer Biology and Genetics Program, Sloan Kettering Institute, New York, NY, USA;Cancer Biology and Genetics Program, Sloan Kettering Institute, New York, NY, USA;Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA;Dana-Farber Cancer Institute and Boston Children’s Hospital, Boston, MA, USA;Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA;Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA;Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA;Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA;Weill Cornell Medical College, Cornell University, New York, NY, USA;Program in Bioinformatics and Integrative Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA;

关键词: Inverted Terminal Repeat;    Thioguanine;    HPRT1 Gene;    Recombination Signal Sequence;    Short Tandem Repeat Analysis;   

DOI  :  10.1186/s12864-016-2877-x

 received in 2016-05-06, accepted in 2016-07-05,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundNumerous human genes encode potentially active DNA transposases or recombinases, but our understanding of their functions remains limited due to shortage of methods to profile their activities on endogenous genomic substrates.ResultsTo enable functional analysis of human transposase-derived genes, we combined forward chemical genetic hypoxanthine-guanine phosphoribosyltransferase 1 (HPRT1) screening with massively parallel paired-end DNA sequencing and structural variant genome assembly and analysis. Here, we report the HPRT1 mutational spectrum induced by the human transposase PGBD5, including PGBD5-specific signal sequences (PSS) that serve as potential genomic rearrangement substrates.ConclusionsThe discovered PSS motifs and high-throughput forward chemical genomic screening approach should prove useful for the elucidation of endogenous genome remodeling activities of PGBD5 and other domesticated human DNA transposases and recombinases.

【 授权许可】

CC BY   
© The Author(s). 2016