| Title | Forward genetic screen of human transposase genomic rearrangements. |
| Publication Type | Journal Article |
| Year of Publication | 2016 |
| Authors | Henssen AG, Jiang E, Zhuang J, Pinello L, Socci ND, Koche R, Gönen M, Villasante CM, Armstrong SA, Bauer DE, Weng Z, Kentsis A |
| Journal | BMC Genomics |
| Volume | 17 |
| Pagination | 548 |
| Date Published | 2016 Aug 04 |
| ISSN | 1471-2164 |
| Keywords | Base Sequence, Cell Line, Gene Expression, Gene Rearrangement, Genetic Testing, Genome, Human, Genomics, High-Throughput Nucleotide Sequencing, Humans, Hypoxanthine Phosphoribosyltransferase, Mutation, Protein Sorting Signals, Sequence Analysis, DNA, Transposases |
| 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. |
| DOI | 10.1186/s12864-016-2877-x |
| Alternate Journal | BMC Genomics |
| PubMed ID | 27491780 |
| PubMed Central ID | PMC4973553 |
| Grant List | K08 CA160660 / CA / NCI NIH HHS / United States K08 DK093705 / DK / NIDDK NIH HHS / United States K99 HG008399 / HG / NHGRI NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States |
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