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.

journal_name

BMC Genomics

journal_title

BMC genomics

authors

Henssen AG,Jiang E,Zhuang J,Pinello L,Socci ND,Koche R,Gonen M,Villasante CM,Armstrong SA,Bauer DE,Weng Z,Kentsis A

doi

10.1186/s12864-016-2877-x

subject

Has Abstract

pub_date

2016-08-04 00:00:00

pages

548

issn

1471-2164

pii

10.1186/s12864-016-2877-x

journal_volume

17

pub_type

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