title: Forward genetic screen of human transposase genomic rearrangements.
abstract: 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.
  
  
  
  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 the HPRT1 mutational spectrum induced by the human transposase PGBD5, including PGBD5-specific signal sequences (PSS) that serve as potential genomic rearrangement substrates.
  
  
  
  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.
authors: Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors: Anton G
authors: AG
authors: Henssen
authors: Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors: Eileen
authors: E
authors: Jiang
authors: Program in Bioinformatics and Integrative Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA.
authors: Jiali
authors: J
authors: Zhuang
authors: Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA, USA.
authors: Luca
authors: L
authors: Pinello
authors: Bioinformatics Core, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors: Nicholas D
authors: ND
authors: Socci
authors: Cancer Biology and Genetics Program, Sloan Kettering Institute, New York, NY, USA.
authors: Richard
authors: R
authors: Koche
authors: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors: Mithat
authors: M
authors: Gonen
authors: Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors: Camila M
authors: CM
authors: Villasante
authors: Cancer Biology and Genetics Program, Sloan Kettering Institute, New York, NY, USA.|Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors: Scott A
authors: SA
authors: Armstrong
authors: Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA, USA.
authors: Daniel E
authors: DE
authors: Bauer
authors: Program in Bioinformatics and Integrative Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA.
authors: Zhiping
authors: Z
authors: Weng
authors: Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA. kentsisresearchgroup@gmail.com.|Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. kentsisresearchgroup@gmail.com.|Weill Cornell Medical College, Cornell University, New York, NY, USA. kentsisresearchgroup@gmail.com.
authors: Alex
authors: 0000-0002-8063-9191
authors: A
authors: Kentsis
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D015870:Gene Expression; D015321:Gene Rearrangement; D005820:Genetic Testing; D015894:Genome, Human; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000737:chemistry / Q000235:genetics; D009154:Mutation; D021382:Protein Sorting Signals / Q000235:genetics; D017422:Sequence Analysis, DNA; D019895:Transposases / Q000737:chemistry / Q000235:genetics*
chemical_list: D021382:Protein Sorting Signals; D007041:Hypoxanthine Phosphoribosyltransferase; C000608604:PGBD5 protein, human; D019895:Transposases