Effect of Disease-Associated Germline Mutations on Structure Function Relationship of DNA Methyltransferases

被引:18
作者
Norvil, Allison B. [1 ]
Saha, Debapriya [1 ]
Dar, Mohd Saleem [1 ]
Gowher, Humaira [1 ]
机构
[1] Purdue Univ, Dept Biochem, W Lafayette, IN 47907 USA
关键词
ADCA-DN; HSAN1E; TBRS; dwarfism; DNMT3A; DNMT1; rare diseases; PCC; PGL; DNA methylation; ACUTE MYELOID-LEUKEMIA; BROWN-RAHMAN SYNDROME; DE-NOVO METHYLATION; OVERGROWTH SYNDROME; CATALYTIC-ACTIVITY; CEREBELLAR-ATAXIA; DNMT3B MUTATIONS; ICF SYNDROME; PWWP DOMAIN; GENE;
D O I
10.3390/genes10050369
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Despite a large body of evidence supporting the role of aberrant DNA methylation in etiology of several human diseases, the fundamental mechanisms that regulate the activity of mammalian DNA methyltransferases (DNMTs) are not fully understood. Recent advances in whole genome association studies have helped identify mutations and genetic alterations of DNMTs in various diseases that have a potential to affect the biological function and activity of these enzymes. Several of these mutations are germline-transmitted and associated with a number of hereditary disorders, which are potentially caused by aberrant DNA methylation patterns in the regulatory compartments of the genome. These hereditary disorders usually cause neurological dysfunction, growth defects, and inherited cancers. Biochemical and biological characterization of DNMT variants can reveal the molecular mechanism of these enzymes and give insights on their specific functions. In this review, we introduce roles and regulation of DNA methylation and DNMTs. We discuss DNMT mutations that are associated with rare diseases, the characterized effects of these mutations on enzyme activity and provide insights on their potential effects based on the known crystal structure of these proteins.
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页数:16
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