This entry represents type 4 UBZ found in RAD18. The domain is a potential zinc finger for nucleic acid binding and a putative nucleotide binding sequence [ (PUBMED:2970061) ]. Human RAD18 accumulates very rapidly and remains for a long period of time at sites of different types of DNA damage, and is required of DNA. RAD18 appears to respond to DNA damage in two distinct ways: replication-dependent and replication-independent. The RAD18-type zinc finger located in the middle of RAD18 is responsible for the replication-independent accumulation of RAD18 following DNA damage, while a second zinc finger, SAP-type, is responsible for replication-dependent accumulation [ (PUBMED:16980296) ].
The ubiquitin-binding zinc finger (UBZ) is a type of zinc-coordinating beta- beta-alpha fold domain found mainly in proteins involved in DNA repair and transcriptional regulation. UBZ domains coordinate a zinc ion with cysteine or histidine residues; depending on their amino acid sequence, UBZ domains are classified into several families [ (PUBMED:19213613) (PUBMED:27062441) ]. Type 1 UBZs are CCHH-type zinc fingers found in tandem UBZ domains of TAX1-binding protein 1 (TAX1BP1) [ (PUBMED:24239949) (PUBMED:26506893) (PUBMED:27370208) ], type 2 UBZs are CCHC-type zinc fingers found in FAAP20 which is a subunit of the Fanconi anemia (FA) core complex [ (PUBMED:25414354) (PUBMED:25799058) ], type 3 UBZs are CCHH-type zinc fingers found only in the Y-family translesion polymerase eta [ (PUBMED:17304240) (PUBMED:17550419) (PUBMED:20837403) ], and type 4 UBZs are CCHC-type zinc fingers found in Y-family translesion polymerase kappa, Werner helicase-interacting protein 1 (WRNIP1), and Rad18 [ (PUBMED:20385554) (PUBMED:25162118) (PUBMED:24794496) ].
The UBZ domain consists of two short antiparallel beta-strands followed by one alpha-helix. The alpha-helix packs against the beta-strands with a zinc ion sandwiched between the alpha-helix and the beta-strands. The zinc ion is coordinated by two cysteines located on the fingertip formed by the beta- strands and two histidines [ (PUBMED:19213613) (PUBMED:17304240) ] or one hisidine and one cysteine [ (PUBMED:25414354) ] on the alpha-helix [ (PUBMED:27062441) ].
Characterization of mRAD18Sc, a mouse homolog of the yeast postreplication repair gene RAD18.
Genomics. 2000; 69: 86-94
Display abstract
The RAD18 gene of the yeast Saccharomyces cerevisiae encodes a protein with ssDNA binding activity that interacts with the ubiquitin-conjugating enzyme RAD6 and plays an important role in postreplication repair. We identified and characterized the putative mouse homolog of RAD18, designated mRAD18Sc. The mRAD18Sc open reading frame encodes a 509-amino-acid polypeptide that is strongly conserved in size and sequence between yeast and mammals, with specific conservation of the RING-zinc-finger and the classic zinc-finger domain. The degree of sequence conservation between mRAD18Sc, RAD18, and homologous sequences identified in other species (NuvA from Aspergillus nidulans and Uvs-2 from Neurospora crassa) is entirely consistent with the evolutionary relationship of these organisms, strongly arguing that these genes are one another's homologs. Consistent with the presence of a nuclear translocation signal in the amino acid sequence, we observed the nuclear localization of GFP-tagged mRAD18Sc after stable transfection to HeLa cells. mRNA expression of mRAD18Sc in the mouse was observed in thymus, spleen, brain, and ovary, but was most pronounced in testis, with the highest level of expression in pachytene-stage primary spermatocytes, suggesting that mRAD18Sc plays a role in meiosis of spermatogenesis. Finally, we mapped the mRAD18Sc gene on mouse chromosome 6F.
The Saccharomyces cerevisiae RAD18 gene encodes a protein that contains potential zinc finger domains for nucleic acid binding and a putative nucleotide binding sequence.
Nucleic Acids Res. 1988; 16: 7119-31
Display abstract
The RAD18 gene of Saccharomyces cerevisiae is required for postreplication repair of UV damaged DNA. We have isolated the RAD18 gene, determined its nucleotide sequence and examined if deletion mutations of this gene show different or more pronounced phenotypic effects than the previously described point mutations. The RAD18 gene open reading frame encodes a protein of 487 amino acids, with a calculated molecular weight of 55,512. The RAD18 protein contains three potential zinc finger domains for nucleic acid binding, and a putative nucleotide binding sequence that is present in many proteins that bind and hydrolyze ATP. The DNA binding and nucleotide binding activities could enable the RAD18 protein to bind damaged sites in the template DNA with high affinity. Alternatively, or in addition, RAD18 protein may be a transcriptional regulator. The rad18 deletion mutation resembles the previously described point mutations in its effects on viability, DNA repair, UV mutagenesis, and sporulation.
