Mutation-induced DNMT1 cleavage drives neurodegenerative disease.
Ontology highlight
ABSTRACT:
SUBMITTER: Wang W
PROVIDER: S-EPMC8442919 | biostudies-literature | 2021 Sep
REPOSITORIES: biostudies-literature
Publications
Mutation-induced DNMT1 cleavage drives neurodegenerative disease.
Wang Wencai W Zhao Xingsen X Shao Yanjiao Y Duan Xiaoya X Wang Yaling Y Li Jialun J Li Jiwen J Li Dali D Li Xuekun X Wong Jiemin J
Science advances 20210901 36
Specific mutations within the replication foci targeting sequence (RFTS) domain of human DNMT1 are causative of two types of adult-onset neurodegenerative diseases, HSAN1E and ADCA-DN, but the underlying mechanisms are largely unknown. We generated <i>Dnmt1-M1</i> and <i>Dnmt1-M2</i> knock-in mouse models that are equivalent to Y495C and D490E-P491Y mutation in patients with HSAN1E, respectively. We found that both mutant heterozygous mice are viable, have reduced DNMT1 proteins, and exhibit neu ...[more]
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