Ask about this productRelated genes to: RAD18 antibody
- Gene:
- RAD18 NIH gene
- Name:
- RAD18 E3 ubiquitin protein ligase
- Previous symbol:
- -
- Synonyms:
- RNF73
- Chromosome:
- 3p25.3
- Locus Type:
- gene with protein product
- Date approved:
- 2003-07-01
- Date modifiied:
- 2019-01-21
Related products to: RAD18 antibody
Related articles to: RAD18 antibody
- Aim: Validate the association RAD18 Arg302Gln (rs373572) and OGG1 Ser326Cys (rs1052133) - with Renal Cell Carcinoma (RCC) susceptibility and histopathological characterization. - Source: PubMed
Altemimi Iftikhar Khdhair AbbasAmeen Binan Adil MohammedAl-Terehi Mona NHussein Liwaa Mahdi - DNA-damage tolerance (DDT) is a highly regulated pathway to resume DNA synthesis in the presence of replication-blocking lesions. In budding yeast , DDT is mediated by sequential ubiquitination and sumoylation of proliferating cell nuclear antigen (PCNA). Rad18 and Rad5 are two E3 ligases responsible for PCNA mono- and poly-ubiquitination, respectively, at its K164 residue. Although Rad18 and Rad5 have been reported to interact with PCNA, they do not contain known PCNA-binding domains like a PCNA interaction peptide (PIP) box. In this study, we performed extensive mapping by a yeast two-hybrid assay and delineated PCNA-binding regions within 40 residues in both Rad18 and Rad5; amino acid sequence alignment revealed that they share a previously uncharacterized sequence defined as a LxLF motif in this study. Interestingly, Rad5 and Rad18 interact with PCNA on same surface distinct from the PIP box-binding sites. Site-specific mutagenesis confirmed that this LxLF motif is required for the DDT functions of Rad18 and Rad5 possibly through affecting PCNA mono- and poly-ubiquitination, respectively. In addition, an adjacent HIRAN domain in Rad5, known to bind 3' DNA ends to drive replication fork reversal, is also required for the PCNA interaction and DDT functions, consistent with previous reports. - Source: PubMed
Publication date: 2026/02/26
Fan LiDu YingNovecosky AllisonLuo YuXiao Wei - Synthetic lethality offers opportunities to identify therapeutic targets for cancer research, facilitating the development of targeted tumour therapy protocols. However, current gene knockout approaches may cause compensatory changes in cellular function and, often, RNAi does not align with the ideal time window for studies and can be inconsistent, limiting the study of molecular interactions, especially when the disruption of two genes causes cell death. To circumvent this problem, we developed the IGIS (Inducible Gene-Inactivation Systems) platform, which uses transient or targeted integration of tetracycline-regulated gene-silencing constructs into human cell lines and fluorescent markers, permitting precise timing of gene inactivation, avoiding transfection variability, and enabling follow-up assays. The applicability of the IGIS systems was validated by investigating the functional interplay between the and genes. Combining IGIS with cell survival, DNA fibre, BrdU alkaline comet assays, and pRPA immunostaining, we show that BRCA1 and RAD18 work in different pathways in replication-fork restart and post-replicative gap filling, and thus combined loss of these factors leads to accumulation of ssDNA gaps and replication catastrophe. This synthetic-lethal interaction study with our newly developed IGIS method highlights RAD18-dependent tolerance mechanisms as potential therapeutic vulnerabilities in BRCA-deficient tumours. - Source: PubMed
Publication date: 2026/02/23
Sánta Ádám TamásGráf AlexandraVincze-Kontár KatalinKovács KatalinBóna BernadettMórocz MónikaKiss ErnőHaracska Lajos - - Source: PubMed
Publication date: 2026/02/09
- The DNA repair protein RAD18 activates "Y-family" -lesion synthesis (TLS) DNA polymerases that are DNA damage-tolerant and potentially error-prone. RAD18 is also frequently overexpressed and pathologically activated in cancer cells. However, the extent to which RAD18 shapes cancer genomes and impacts tumorigenesis is unclear. Therefore, we tested the effect of status on chemically induced and oncogene-driven tumorigenesis. In a chemically induced oral carcinogenesis model, acute (2-16 days) 4NQO treatment induces expression of and TLS polymerase mRNAs in mouse oral epithelial cells prior to the emergence of oral squamous cell carcinomas (OSCCs). Chronic (8-week) 4NQO treatment leads to the onset of oral tumors that is accelerated in mice when compared with animals. Analysis of OSCC exomes reveals increased levels of G(C)>T(A) transversions in tumors when compared with . Therefore, Rad18 promotes error-free bypass of 4NQO-induced DNA lesions and suppresses 4NQO-induced oral carcinogenesis. In a -induced lung carcinogenesis model, deficiency did not affect rates or incidence of oncogene-induced lung tumors or mutations. Taken together, we demonstrate that Rad18 has context-specific tumor-suppressive activity. Given the prevalence of 4NQO-like environmental exposures, RAD18 is highly likely to shape human cancer genomes and perhaps influence other aspects of the tumorigenic process. - Source: PubMed
Publication date: 2026/01/19
Anand Jay RBrown Bethany WagnerLou JitongGu QishengYang YangDroby GaithWu DiJena AkankshyaXie JialiuFedoriw YuriWeissman BernardWilliams ScottVaziri Cyrus