[HTML][HTML] Forward genetic screen of human transposase genomic rearrangements

AG Henssen, E Jiang, J Zhuang, L Pinello, ND Socci… - BMC genomics, 2016 - Springer
AG Henssen, E Jiang, J Zhuang, L Pinello, ND Socci, R Koche, M Gonen, CM Villasante…
BMC genomics, 2016Springer
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 …
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.
Springer