2. Academic Validation
  3. Forward genetic screen of human transposase genomic rearrangements

Forward genetic screen of human transposase genomic rearrangements

  • BMC Genomics. 2016 Aug 4;17:548. doi: 10.1186/s12864-016-2877-x.
Anton G Henssen 1,  Eileen Jiang 1,  Jiali Zhuang 2,  Luca Pinello 3,  Nicholas D Socci 4,  Richard Koche 5,  Mithat Gonen 6,  Camila M Villasante 1,  Scott A Armstrong 5 7,  Daniel E Bauer 3,  Zhiping Weng 2,  Alex Kentsis 8 9 10
Affiliations

Affiliations

  • 1 Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 2 Program in Bioinformatics and Integrative Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA.
  • 3 Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA, USA.
  • 4 Bioinformatics Core, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 5 Cancer Biology and Genetics Program, Sloan Kettering Institute, New York, NY, USA.
  • 6 Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
  • 7 Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 8 Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA. kentsisresearchgroup@gmail.com.
  • 9 Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. kentsisresearchgroup@gmail.com.
  • 10 Weill Cornell Medical College, Cornell University, New York, NY, USA. kentsisresearchgroup@gmail.com.
PMID: 27491780 DOI: 10.1186/s12864-016-2877-x
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 the HPRT1 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.

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