Forward genetic screen of human transposase genomic rearrangements Journal Article

Authors: Henssen, A. G.; Jiang, E.; Zhuang, J.; Pinello, L.; Socci, N. D.; Koche, R.; Gonen, M.; Villasante, C. M.; Armstrong, S. A.; Bauer, D. E.; Weng, Z.; Kentsis, A.
Article Title: Forward genetic screen of human transposase genomic rearrangements
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. © 2016 The Author(s).
Keywords: protein expression; gene mutation; sequence analysis; exon; gene; gene expression; cell growth; protein depletion; genetic variability; intron; gene rearrangement; amplicon; fibroblast; dna sequence; genetic screening; complementary dna; growth inhibition; hypoxanthine phosphoribosyltransferase; transposase; dna transposition; human; article; hprt1 gene
Journal Title: BMC Genomics
Volume: 17
Issue: 1
ISSN: 1471-2164
Publisher: Biomed Central Ltd  
Date Published: 2016-08-04
Start Page: 548
Language: English
DOI: 10.1186/s12864-016-2877-x
PROVIDER: scopus
PMCID: PMC4973553
PUBMED: 27491780
Notes: Article -- Export Date: 1 September 2016 -- Source: Scopus
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MSK Authors
  1. Mithat Gonen
    721 Gonen
  2. Nicholas D Socci
    188 Socci
  3. Scott Allen Armstrong
    108 Armstrong
  4. Richard Patrick Koche
    52 Koche
  5. Alex   Kentsis
    52 Kentsis
  6. Eileen   Jiang
    5 Jiang