The mus-8 gene of Neurospora crassa encodes a structural and functional homolog of the Rad6 protein of Saccharomyces cerevisiae

Abstract

We cloned a DNA repair gene, mus-8, of Neurospora crassa and sequenced the genomic DNA and cDNA. Nucleotide-sequence analysis indicated that the mus-8 gene contains an open reading frame (ORF) of 456 bp, interrupted by three small introns. The deduced amino-acid sequence showed that the mus-8 gene encodes a 17 kDa protein which has 77.5% and 83.3% identity to the Rad6 protein of Saccharomyces cerevisiae and the rhp6(+) protein of Schizosaccharomyces pombe, respectively. The Rad6 protein is a ubiquitin-conjugating enzyme (E2) and is required for DNA repair, mutagenesis, and sporulation in yeast. Introduction of the mus-8 gene into a S. cerevisiae rad6 mutant resulted in significant recovery of DNA repair functions, especially UV-mutagenesis, and also sporulation, both of which are defective in the rad6 mutant. It is therefore postulated that mus-8 of Neurospora has a function very similar to that demonstrated for RAD6 of S. cerevisiae.

Dysfunction of human Rad18 results in defective postreplication repair and hypersensitivity to multiple mutagens

“…1B). However, hRAD18 and uvs-2 do not have the nucleotide-binding motif that is found in yeast RAD18 (7,8). Despite the high similarity between RAD18 and uvs-2, the uvs-2 gene cannot complement yeast rad18 mutant (7,8).…”

“…A homologue of RAD18 has been identified from the filamentous fungus Neurospora crassa. This gene, uvs-2, encodes a protein that shares 25.5% amino acid identity with Rad18 and interacts with a Rad6 homologue, MUS8 (7,8). In contrast to the yeast rad18 mutant, the uvs-2 mutant shows high mutation frequencies under both spontaneous and induced conditions (9)(10)(11).…”

The Genomes of Three Uneven Siblings: Footprints of the Lifestyles of Three Trichoderma Species

“…In T. reesei, T. atroviride, and T. virens, three putative E2 ubiquitin-conjugating enzymes were identified, and only one of them is a Rad6-like protein (see Table S1 in the supplemental material). It has been reported that the Rad6p protein of S. cerevisiae, the Rhp6 protein of S. pombe, and MUS-8 of N. crassa have a very similar function (284). Therefore, it can be assumed that the Trichoderma Rad6-like proteins (TR_120075, TA_301071, and TV_81725) are involved in DNA repair functions, especially UVinduced mutagenesis, and also in sporulation.…”

Lessons from the Genome Sequence ofNeurospora crassa: Tracing the Path from Genomic Blueprint to Multicellular Organism

“…Neurospora has several predicted subunits of ubiquitin-activating (E1) and ubiquitin-ligating (E2) proteins that are predicted to be involved in histone ubiquitylation. For example, the Neurospora mus-8 gene encodes a Rad6p-like H2B ubiquitin-ligase (Table 5) (658,749). This enzyme affects gene silencing via histone H3 methylation states in S. cerevisiae, an example of "trans-tail" regulation of histone modifications (765).…”