Forward genetic screen of human transposase genomic rearrangements. (December 2016)

• Record Type: Journal Article
• Authors: Henssen, Anton; Jiang, Eileen; Zhuang, Jiali; Pinello, Luca; Socci, Nicholas; Koche, Richard; Gonen, Mithat; Villasante, Camila; Armstrong, Scott; Bauer, Daniel; Weng, Zhiping; Kentsis, Alex
• Is Part Of: BMC genomics. Volume 17:Number 1(2016)
• Page Start: 1
• Page End: 9
• Publication Date: 2016-12
• Subjects: Genomes -- Periodicals; Gene mapping -- Periodicals; Genomics -- Periodicals; Base Sequence -- Periodicals; Chromosome Mapping -- Periodicals; Genetic Techniques -- Periodicals; Sequence Analysis, DNA -- Periodicals; 572.8605
• DOI: 10.1186/s12864-016-2877-x
• Languages: English
• ISSNs: 1471-2164

Abstract

Abstract Background Numerous 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. Results To 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 theHPRT1 mutational spectrum induced by the human transposase PGBD5, including PGBD5-specific signal sequences (PSS) that serve as potential genomic rearrangement substrates. Conclusions The 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.