Disease relevance of RNR4

• Simultaneous overexpression of RNR2, RNR3 and RNR4 partially rescued the HU hypersensitivity of a ccr4Delta dun1Delta strain, consistent with the notion that the RNR genes are key targets of Crt1 [1].

High impact information on RNR4

• Here, we report the isolation of the WTM (WD40-containing transcriptional modulator) proteins as regulators of Rnr2/Rnr4 localization [2].
• Forced localization of Wtm1 to the nucleolus causes Rnr2/Rnr4 complexes to relocalize to the nucleolus [2].
• During S phase and in response to DNA damage, Rnr2-Rnr4 enters the cytoplasm, where it presumably combines with Rnr1 to form an active complex [2].
• The specific activity of the Rnr2p complexed with Rnr4p is 2,250 nmol deoxycytidine 5'-diphosphate formed per min per mg, whereas the homodimer of Rnr2p shows no activity [3].
• The sensitivity of snf1 to HU or to RNR4 deletion may be due to posttranscriptional defects in RNR function or to defects in the repair of, and recovery from, stalled replication forks [4].

Biological context of RNR4

• As is the case for the other RNR genes, RNR4 is induced by agents that damage DNA [5].
• We have cloned a second essential gene encoding a homologous small subunit, RNR4 [6].
• The central role of RNR in DNA precursor metabolism and its complex regulation allow for several modes of suppression that may influence the phenotypes of RNR4 mutants, especially those containing the leaky pso3-1 mutant allele [7].
• Both RNR4 mutant alleles confer significantly less sensitivity to UVC than mutant alleles of non-UVC-mutable REV3, indicating that, apart from nucleotide excision repair, RAD6-dependent error-free DNA repair may still be functional [7].
• This base substitution was localized within the domain of exon 4 encoding the RR small subunit signature, and causes an amino acid substitution in one of the most highly conserved regions of p53R2, in which human R2 and yeast RNR2 and RNR4 proteins are highly homologous [8].

Associations of RNR4 with chemical compounds

• However, Rnr4p lacks a number of sequence elements thought to be essential for iron binding, and mutation of the critical tyrosine residue does not affect Rnr4p function [5].
• Cloning and sequencing of the RNR4 locus of the pso3-1 mutant revealed that its intermediate phenotype is attributable to a G --> A transition at nucleotide 352, leading to replacement of glycine by arginine [G118R] in the mutant's protein [7].

Regulatory relationships of RNR4

• The lethality of RNR4 deletion mutations can be suppressed by overexpression of RNR1 and RNR3, two genes encoding the large subunit of the RNR enzyme, indicating genetic interactions among the RNR genes [6].
• Nevertheless, Rnr4 is required to activate Rnr2, and the functional species in vivo is believed to be a heterodimeric complex between the two proteins [9].

Other interactions of RNR4

• Rnr4p, a novel ribonucleotide reductase small-subunit protein [5].
• Overproduction of Wtm2 increased Rnr2/Rnr4 [2].
• The N-terminal acetylation status of Tfs1p, Act1p, and Rnr4p in both wild type and nat3Delta was confirmed by tandem mass spectrometry [10].

References