The LSH/DDM1 Homolog MUS-30 Is Required for Genome Stability, but Not for DNA Methylation in Neurospora crassa

PLoS Genetics
Evelina Y BasenkoZachary A Lewis

Abstract

LSH/DDM1 enzymes are required for DNA methylation in higher eukaryotes and have poorly defined roles in genome maintenance in yeast, plants, and animals. The filamentous fungus Neurospora crassa is a tractable system that encodes a single LSH/DDM1 homolog (NCU06306). We report that the Neurospora LSH/DDM1 enzyme is encoded by mutagen sensitive-30 (mus-30), a locus identified in a genetic screen over 25 years ago. We show that MUS-30-deficient cells have normal DNA methylation, but are hypersensitive to DNA damaging agents. MUS-30 is a nuclear protein, consistent with its predicted role as a chromatin remodeling enzyme, and levels of MUS-30 are increased following DNA damage. MUS-30 co-purifies with Neurospora WDR76, a homolog of yeast Changed Mutation Rate-1 and mammalian WD40 repeat domain 76. Deletion of wdr76 rescued DNA damage-hypersensitivity of Δmus-30 strains, demonstrating that the MUS-30-WDR76 interaction is functionally important. DNA damage-sensitivity of Δmus-30 is partially suppressed by deletion of methyl adenine glycosylase-1, a component of the base excision repair machinery (BER); however, the rate of BER is not affected in Δmus-30 strains. We found that MUS-30-deficient cells are not defective for DSB repair, ...Continue Reading

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Citations

Apr 7, 2017·Nucleic Acids Research·Ireneusz LitwinRobert Wysocki
May 14, 2016·G3 : Genes - Genomes - Genetics·Michael SeymourZachary A Lewis
Jan 21, 2021·Proceedings of the National Academy of Sciences of the United States of America·Masayuki KameiZachary A Lewis
Apr 10, 2021·Nature Cell Biology·Paul B Talbert, Steven Henikoff
Sep 17, 2021·Scientific Reports·Yong LiWioletta Czaja

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Datasets Mentioned

BETA
GSE70518

Methods Mentioned

BETA
MethylC-seq
electrophoresis
affinity purifications
gene knockout
affinity purification
PCR

Software Mentioned

BLAST

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