Disease relevance of RAD14

• Yeast RAD14 and human xeroderma pigmentosum group A DNA-repair genes encode homologous proteins [1].
• However, a significant enhancement in toxicity and mutagenicity was observed when cells lacked both Rad14 and Mag1 [2].

High impact information on RAD14

• Importantly, the abolishment of NER, by abrogation of RAD1 or RAD14, completely stopped repair of UV damage even during G2/M phase [3].
• The post-UV histone modifications and chromatin remodeling at the repressed MFA2 promoter do not activate MFA2 transcriptionally, nor do they require damage recognition by Rad4p or Rad14p [4].
• Rad1-Rad10 forms a ternary complex with the DNA damage recognition protein Rad14, providing a means for targeting this nuclease to the damage site [5].
• Removal of cyclobutane pyrimidine dimers from damaged DNA by enzymatic photoreactivation has no effect on binding, strongly suggesting that RAD14 recognizes pyrimidine(6-4)pyrimidone photoproduct sites [6].
• To examine this model further, we have constructed a histidine-tagged version of the yeast DNA damage recognition protein Rad14 [7].

Biological context of RAD14

• To accomplish this, we have deleted one of the genes essential for NER in yeast, namely, RAD14, both in the context of an otherwise DNA repair-proficient strain (Deltarad14) and in a BER-defective isogenic derivative lacking the MAG1 gene (Deltamag1rad14) [2].
• The second assay uses the apn1 apn2 rad14 triple mutant, which is viable but exhibits a spontaneous mutator phenotype [8].
• Yeast DNA repair protein RAD23 promotes complex formation between transcription factor TFIIH and DNA damage recognition factor RAD14 [9].
• The results also indicate that monoadduct formation by CDDP or 8-MOP at the doses used is not sufficient to delay S-phase in the rad14 Delta mutant [10].
• S-phase delay was not observed after ICL damage introduced by cisplatin (CDDP) or 8-methoxypsoralen (8-MOP) during the G1-phase, in any of the above mutants, or in an isogenic rad14 Delta mutant deficient in nucleotide excision repair [10].

Anatomical context of RAD14

• (4) Leaky alleles of rad1, rad3 and rad14 show a very marked difference in repair rates of the two lesions, rather like the human XPA revertant cell line XP129 and the Chinese hamster mutants UV61 and V-H1 [11].

Associations of RAD14 with chemical compounds

• Three additional genes involved in pyrimidine dimer removal in Saccharomyces cerevisiae: RAD7, RAD14 and MMS19 [12].
• Affinity purification and partial characterization of a yeast multiprotein complex for nucleotide excision repair using histidine-tagged Rad14 protein [7].
• However, the psoralen analog angelicin (monoadduct damage) induced a significant S-phase delay in the rad14 Delta mutant [10].
• Looking for mutants specifically defective in activating the checkpoint following UV lesions, but proficient in the response to methyl methane sulfonate and double-strand breaks, we isolated cdu1-1, which is allelic to RAD14, the homolog of human XPA, involved in lesion recognition during nucleotide excision repair (NER) [13].
• Here we report an increased frequency of forward mutation to canavanine resistance in mutants defective in the nucleotide excision repair (NER) gene RAD14 [14].

Other interactions of RAD14

• Low-molecular-weight DNA was observed in rad14 cdc9 and rad16 cdc9 strains [15].
• The RAD4 and RAD14 genes have a particular role in repair following exposure to those ethylating agents that preferentially alkylate oxygen, but not to those that preferentially ethylate nitrogen [16].
• The rad23 mutation does not suppress the high UV sensitivity of completely NER-deficient rad1 or rad14 strains [17].
• Our data indicate that DNA damage is not the main determinant for cell killing by photodynamic treatment and that the type of damage induced is apparently not subject to RAD14- or RAD52 controlled repair [18].
• Complex formation with damage recognition protein Rad14 is essential for Saccharomyces cerevisiae Rad1-Rad10 nuclease to perform its function in nucleotide excision repair in vivo [19].

Analytical, diagnostic and therapeutic context of RAD14

• In DNA mobility-shift assays, RAD14 binds specifically to UV-damaged DNA [6].
• Rad14 was also isolated as a partner of the Ddc1 checkpoint protein in a two-hybrid screening, and physical interaction was proven by co-immunoprecipitation [13].
• By several independent criteria, including co-purification, immunoprecipitation, and gel filtration of homogeneous proteins, we show that the damage recognition factor Rad14 exists in a ternary complex with the Rad1-Rad10 nuclease [20].

References