Disease relevance of REV3L

• Response of human REV3 gene to gastric cancer inducing carcinogen N-methyl-N'-nitro-N-nitrosoguanidine and its role in mutagenesis [1].
• Recently, using PCR tests that amplify REV envelope and REV 3' LTR sequences provided a more accurate assessment of the insertion of REV provirus in FPV than PCR assays that amplify the REV 5' LTR [2].

High impact information on REV3L

• Inhibition of the pol zeta REV3 catalytic subunit by specific phosphorothioate-modified oligonucleotides impaired Ig and bcl-6 hypermutation and UV damage-induced DNA mutagenesis, without affecting cell cycle or viability [3].
• Together with DNA polymerase zeta (Rev3/7), Rev1 function is required for the active introduction of the majority of mutations into the genomes of eukaryotes from yeast to humans [4].
• Cisplatin induced a concentration- and time-dependent increase in hREV3 mRNA [5].
• The results indicate that, following formation of cisplatin adducts in DNA, REV3 mRNA levels increase, and polymerase zeta functions to promote both cell survival and the generation of drug-resistant variants in the surviving population [5].
• Reduction of REV3 mRNA did not alter the rate of cisplatin adduct removal but did impair both spontaneous and cisplatin-induced extrachromosomal homologous recombination and attenuated bypass replication as reflected by reduced ability to express luciferase from a platinated plasmid [5].

Biological context of REV3L

• Alternative splicing, genomic structure, and fine chromosome localization of REV3L [6].
• Recently, the human REV1 (hREV1) and REV3 (hREV3) genes were identified, and their products were revealed to be involved in UV-induced mutagenesis, as observed for their yeast counterparts [7].
• These findings suggest the possibility that hREV7 might play an important role in regulating the enzymatic activities of hREV1 and hREV3 for mutagenesis in response to DNA damage [7].
• In S. cerevisiae, the REV3 gene, encoding the catalytic subunit of polymerase zeta, is involved in translesion synthesis and required for the production of mutations induced by ultraviolet radiation (UV) photoproducts and other DNA fork-blocking lesions, and for the majority of spontaneous mutations [8].
• We have identified human cDNA clones from two different libraries whose deduced amino acid sequences bear remarkable homology to the yeast Rev3, and named this gene hREV3 [9].

Anatomical context of REV3L

• hREV3 is essential for error-prone translesion synthesis past UV or benzo[a]pyrene diol epoxide-induced DNA lesions in human fibroblasts [8].
• The hREV3 encodes an mRNA of >10 kb, and its expression varies in different tissues and appears to be elevated in some but not all of the tumor cell lines we have examined [9].
• The orthologue of Rev3 has been cloned from higher eukaryotic cells, including human, but its role in mutagenesis and carcinogenesis remains obscure [10].
• These mice are viable, have greatly reduced levels of Rev3 transcript, and have reduced levels of B cells and impaired development of high-affinity memory B cells [10].
• Investigation into the cellular function of pol zeta has been hindered by the fact that Rev3 knockout mice do not survive beyond midgestation, and embryonic stem cells used to derive these mice are not genetically stable [10].

Associations of REV3L with chemical compounds

• CONCLUSION: The expression of the human REV3 can be upregulated at the transcriptional level in response to MNNG [1].

Other interactions of REV3L

• Human REV7 (hREV7) was also cloned, and its product was found to interact with hREV3, but the biological function of hREV7 remained unknown [7].
• Identification, chromosomal mapping and tissue-specific expression of hREV3 encoding a putative human DNA polymerase zeta [9].

Analytical, diagnostic and therapeutic context of REV3L

• The hREV3 gene was mapped to chromosome 1p32-33 by fluorescence in situ hybridization [9].
• METHODS: The response of the human REV3 gene to MNNG was measured in human 293 cells and FL cells by RT-PCR [1].
• The blockage effect of REV3 was measured by combination of reverse transcription-polymerase chain reaction to detect the expression of antisense REV3 RNA and Western blotting to detect the REV3 protein level [1].
• A 2570-bp fragment of the 5' flanking region of REV3 gene was amplified by PCR from PAC clone RP3-415N12 and inserted into the pGL3-Basic reporter vector [11].

References