Forward genetic screen of human transposase genomic rearrangements.

Forward genetic screen of human transposase genomic rearrangements.
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人转座酶基因组重排的正向遗传筛查。

DOI:
10.1186/s12864-016-2877-x
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发表时间:
2016-08-04
期刊:
影响因子:
4.4
通讯作者:
Kentsis A
Kentsis A
中科院分区:
生物学2区
文献类型:
--
作者:
Henssen AG;Jiang E;Zhuang J;Pinello L;Socci ND;Koche R;Gonen M;Villasante CM;Armstrong SA;Bauer DE;Weng Z;Kentsis A

文献摘要

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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. 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. 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. The online version of this article (doi:10.1186/s12864-016-2877-x) contains supplementary material, which is available to authorized users.