Forward genetic screen of human transposase genomic rearrangements

人类转座酶基因组重排的正向遗传学筛选

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作者:Anton G Henssen, Eileen Jiang, Jiali Zhuang, Luca Pinello, Nicholas D Socci, Richard Koche, Mithat Gonen, Camila M Villasante, Scott A Armstrong, Daniel E Bauer, Zhiping Weng, Alex Kentsis

Background

Numerous human genes encode potentially active DNA transposases or recombinases, but our understanding of their functions remains limited due to shortage of

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.

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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