High-throughput synthetic rescue for exhaustive characterization of suppressor mutations in human genes View Full Text


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Article Info

DATE

2020-04-08

AUTHORS

Farah Kobaisi, Nour Fayyad, Eric Sulpice, Bassam Badran, Hussein Fayyad-Kazan, Walid Rachidi, Xavier Gidrol

ABSTRACT

Inherited or acquired mutations can lead to pathological outcomes. However, in a process defined as synthetic rescue, phenotypic outcome created by primary mutation is alleviated by suppressor mutations. An exhaustive characterization of these mutations in humans is extremely valuable to better comprehend why patients carrying the same detrimental mutation exhibit different pathological outcomes or different responses to treatment. Here, we first review all known suppressor mutations’ mechanisms characterized by genetic screens on model species like yeast or flies. However, human suppressor mutations are scarce, despite some being discovered based on orthologue genes. Because of recent advances in high-throughput screening, developing an inventory of human suppressor mutations for pathological processes seems achievable. In addition, we review several screening methods for suppressor mutations in cultured human cells through knock-out, knock-down or random mutagenesis screens on large scale. We provide examples of studies published over the past years that opened new therapeutic avenues, particularly in oncology. More... »

PAGES

4209-4222

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00018-020-03519-6

    DOI

    http://dx.doi.org/10.1007/s00018-020-03519-6

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/32270227


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    36 schema:description Inherited or acquired mutations can lead to pathological outcomes. However, in a process defined as synthetic rescue, phenotypic outcome created by primary mutation is alleviated by suppressor mutations. An exhaustive characterization of these mutations in humans is extremely valuable to better comprehend why patients carrying the same detrimental mutation exhibit different pathological outcomes or different responses to treatment. Here, we first review all known suppressor mutations’ mechanisms characterized by genetic screens on model species like yeast or flies. However, human suppressor mutations are scarce, despite some being discovered based on orthologue genes. Because of recent advances in high-throughput screening, developing an inventory of human suppressor mutations for pathological processes seems achievable. In addition, we review several screening methods for suppressor mutations in cultured human cells through knock-out, knock-down or random mutagenesis screens on large scale. We provide examples of studies published over the past years that opened new therapeutic avenues, particularly in oncology.
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