Disease relevance of RAD3

• Drug toxicity was marginally increased by the presence of rad3 and rad18 mutations [1].
• Significant amino acid homology is observed with yeast RAD3 and E. coli UvrD (helicase II) proteins which are required for excision repair of damaged DNA [2].

High impact information on RAD3

• The 85 kd and 50 kd subunits of factor b are now identified as RAD3 and SSL1 proteins, respectively; both are known to be involved in DNA repair [3].
• DNA repair gene RAD3 of S. cerevisiae is essential for transcription by RNA polymerase II [4].
• The RAD3 gene of Saccharomyces cerevisiae is required for excision repair of ultraviolet-damaged DNA and is essential for cell viability [4].
• Most strikingly, splicing of crs1 and rem1 is regulated by sequences located outside the coding regions, far from the target introns, a phenomenon previously observed only in metazoans [5].
• We show that a transcription-defective allele of the Rad3p helicase, a component of the TFIIH transcription initiation factor, suppresses several phenotypes associated with defective mRNA processing and export [6].

Chemical compound and disease context of RAD3

• Fusions between the RAD3 gene and the lac'Z gene of Escherichia coli were constructed and used to demonstrate that the RAD3 gene was not inducible by DNA damage caused by UV radiation or 4-nitroquinoline-1-oxide [7].
• Conversely, E. coli helicase II is highly sensitive to noncovalent DNA modifications but less sensitive than Rad3 protein to ultraviolet radiation damage or cisplatin adducts [8].

Biological context of RAD3

• Nucleotide sequence analysis of CHL1 revealed a 2.6 kb open reading frame with a 99 kd predicted protein sequence that contained two PEST sequences and was 23% identical to the coding region of a nucleotide excision repair gene, RAD3 [9].
• A yeast strain was constructed that had a disruption of the chromosomal RAD3 gene and carried a series of centromeric plasmids with defined mutations in this gene [10].
• The mutator phenotype suggests that the wild-type RAD3 gene product may be involved in the maintenance of fidelity of DNA replication in addition to its known role in excision repair [11].
• To investigate the role that RAD3 might play in mutation avoidance, we have utilized a well-characterized shuttle vector system to study the mutational spectrum occurring in rad3-102 strains and compare it to that seen in RAD3 strains [11].
• In addition to its role in nucleotide excision repair, the RAD3 gene is essential for the viability of haploid cells in the absence of DNA damage [12].

Anatomical context of RAD3

• These results were not observed when RAD10 was introduced into excision repair-defective CHO cell lines from other genetic complementation groups, nor when the yeast RAD3 gene was expressed in cells from genetic complementation group 2 [13].

Associations of RAD3 with chemical compounds

• The product of the RAD3 gene of Saccharomyces cerevisiae is required for mitotic cell viability and excision repair of UV-induced pyrimidine dimers [11].
• Our results indicate that the RAD3 gene is required for DDRA2 transcript production following NQO or MNNG treatments [14].
• RAD3 and RAD52 genes act independently in processing DNA damage induced by high concentrations of bleomycin [15].
• Mutation of lysine-48 to arginine in the yeast RAD3 protein abolishes its ATPase and DNA helicase activities but not the ability to bind ATP [16].
• The sequence Gly-X-Gly-Lys-Thr, believed to be involved in the interaction with purine nucleotides in proteins that bind and hydrolyze the nucleotides, is present in the RAD3 primary structure between amino acids 45 and 49 [16].

Physical interactions of RAD3

• Yeast RAD3 protein binds directly to both SSL2 and SSL1 proteins: implications for the structure and function of transcription/repair factor b [17].
• Substrate specificity of the Rad3 ATPase/DNA helicase of Saccharomyces cerevisiae and binding of Rad3 protein to nucleic acids [18].

Regulatory relationships of RAD3

• In UV-irradiated JG-1 (rad1-1), rad3 and rad11 as well as in DEB-inactivated rad7, rad11, rad19 and rad20 the inability of LHR is a constitutive phenomenon and cannot be overcome by exogenous energy supply [19].
• That the rad3 Arg-48 mutation inactivates the DNA and DNA.RNA helicase activities and confers a substantial reduction in the incision of UV-damaged DNA suggests a role for these activities in incision [20].

Other interactions of RAD3

• The RAD3 and SSL2 gene products are essential proteins that are also required for the nucleotide excision repair pathway [17].
• We found that ssl1, rad3 and tfb1 mutants, like rad25(ssl2-xp) mutants, are deficient in both the global NER and TCR pathways [21].
• Both RAD3 and SIN4 gene products are implicated in the RNA polymerase II transcription process [22].
• The mode of interaction in haploid Saccharomyces cerevisiae of two pso mutations with each other and with rad mutations affected in their excision-resynthesis (rad3), error-prone (rad6), and deoxyribonucleic acid double-strand break (rad52) repair pathways was determined for various double mutant combinations [23].
• Consequently, it is proposed that PSO1 and RAD3 genes govern steps in the independent pathways [23].

Analytical, diagnostic and therapeutic context of RAD3

• We describe the molecular cloning of a 6-kilobase (kb) fragment of yeast chromosomal DNA containing the RAD3 gene of Saccharomyces cerevisiae [24].
• Mutational analysis indicates that the kinase domain is required for Rad3 function, and immunoprecipitation of overexpressed Rad3 demonstrates an associated protein kinase activity [25].
• Relation between liquid-holding recovery, DNA repair, and mitotic recombination in the rad3 mutant of Saccharomyces cerevisiae after treatment with diepoxybutane (DEB) [26].
• We have also constructed new rad3 alleles by oligonucleotide-directed mutagenesis and have tested their effects on spontaneous mutation and mitotic recombination and on UV repair [27].

References