Abstract |
While a plethora of genetic techniques have been developed over the past century, modifying specific sequences of the fruit fly genome has been a difficult, if not impossible task. clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 truly redefined molecular genetics and provided new tools to model human diseases in Drosophila melanogaster. This is particularly true for genes whose protein sequences are highly conserved. Phosphoribosyl pyrophosphate synthetase (PRPS) is a rate-limiting enzyme in nucleotide metabolism whose missense mutations are found in several neurological disorders, including Arts syndrome. In addition, PRPS is deregulated in cancer, particularly those that become resistant to cancer therapy. Notably, Drosophila PRPS shares about 90% protein sequence identity with its human orthologs, making it an ideal gene to study via CRISPR/Cas9. In this review, we will summarize recent findings on PRPS mutations in human diseases including cancer and on the molecular mechanisms by which PRPS activity is regulated. We will also discuss potential applications of Drosophila CRISPR/Cas9 to model PRPS-dependent disorders and other metabolic diseases that are associated with nucleotide metabolism.
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Authors | Keemo Delos Santos, Eunjeong Kwon, Nam-Sung Moon |
Journal | International journal of molecular sciences
(Int J Mol Sci)
Vol. 21
Issue 14
(Jul 08 2020)
ISSN: 1422-0067 [Electronic] Switzerland |
PMID | 32650483
(Publication Type: Journal Article, Review)
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Chemical References |
- Ribose-Phosphate Pyrophosphokinase
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Topics |
- Animals
- Ataxia
(genetics)
- CRISPR-Cas Systems
(genetics)
- Deaf-Blind Disorders
(genetics)
- Disease Models, Animal
- Drosophila melanogaster
(genetics)
- Gene Editing
(methods)
- Genetic Diseases, X-Linked
(genetics)
- Humans
- Mutation
(genetics)
- Ribose-Phosphate Pyrophosphokinase
(genetics)
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