Disease relevance of TRM2

• In contrast to what is found for the tRNA(m5U54)methyltransferase encoding gene trmA+ in E. coli, the TRM2 gene is not essential for cell viability and a deletion strain shows no obvious phenotype [1].
• Identification of a human homologue of yeast nuc2 which interacts with the retinoblastoma protein in a specific manner [2].

High impact information on TRM2

• Other than lacking 5-methyluridine trm2 cells have no obvious physiological defect [3].
• The methylation of U54 is catalyzed by the tRNA(m5U54)methyltransferase, which in Saccharomyces cerevisiae is encoded by the nonessential TRM2 gene [4].
• The expression and activity of the yNucR endo-exonuclease is dependent on the RAD52 gene, and does not respond to increased gene dosage of the RNC1/NUD1 gene [1].
• To mimic the temperature-sensitive mutant of yeast nuc2, an H-NUC mutant was made in which the highly conserved glycine 640 residue was changed to aspartic acid [2].
• Here, we report that transient expression of NUD1 results in up to 62% increase in the frequency of homologous recombination between two co-transfected linear plasmids in mouse Ltk- cells [5].

Biological context of TRM2

• First, a multicopy plasmid (YEp213-10) carrying NUC2 was transformed into a RAD52 strain [6].
• The RHO4a and NUD1 genes on Saccharomyces cerevisiae chromosome XI [7].
• The data show that the phenotype of S. cerevisiae nud1 mutants is characterized by enhanced export of secretory proteins and that the passage of proteins through the walls of nud1 cells is an active process [8].
• Saccharomyces cerevisiae NUD1 gene codes for a spindle pole body component and nud1 temperature-sensitive mutants arrest at 38 degrees C in late anaphase with a tendency for lysis [8].
• While the nud1 strain is only slightly sensitive to ionizing radiation, expression of the HO-endonuclease to introduce a DSB at the MAT locus in that strain results in cell death [9].

Anatomical context of TRM2

• Recently, we have demonstrated that transient expression of Saccharomyces cerevisiae EE NUD1 gene in HeLa cells increased the resistance of the latter to ionizing radiation and cisplatin, suggesting the involvement of the NUD1 gene product in the recombination repair of double-strand breaks (DSB) [5].
• Transient expression of Saccharomyces cerevisiae endo-exonuclease NUD1 gene increases the frequency of extrachromosomal homologous recombination in mouse Ltk- fibroblasts [5].

Associations of TRM2 with chemical compounds

• Second, a strain having a nuc2 allele that encodes a temperature-sensitive nuclease was treated with ethidium bromide at the restrictive and permissive temperatures [6].

Regulatory relationships of TRM2

• The nuclease RhoNuc (previously designated yNucR), encoded by the RNC1 (previously designated NUC2) gene and regulated by the RAD52 gene, is not required for recombination when one substrate is single-stranded but is essential for the majority of recombination events when both substrates are double-stranded [10].

Analytical, diagnostic and therapeutic context of TRM2

• Sequence analysis of a 4 kb fragment from the right arm of Saccharomyces cerevisiae chromosome XI, in combination with Northern hybridization experiments revealed the presence of two genes, designated RHO4a and NUD1 [7].
• From these results we conclude that the proposed RNC1 gene is the result of a cloning artefact and that the yNucR protein is instead encoded by the NUD1 gene [7].
• HeLa cells transiently transfected with a mammalian expression DNA vector expressing the Saccharomyces cerevisiae endo-exonuclease (EE) NUD1 gene have exhibited changes in cell survival frequencies after treatment with different DNA-damaging agents as compared to HeLa cells transfected with a control plasmid [11].
• Polymerase chain reaction analysis showed that many of the nud1 survivors contained small alterations within theMAT locus, suggesting that the survivors arose through the process of non-homologous end-joining [9].

References