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Facts about Exonuclease 1.
Also exhibits endonuclease activity against 5'-overhanging flap structures similar to those generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. Required for somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin genes.
Human | |
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Gene Name: | EXO1 |
Uniprot: | Q9UQ84 |
Entrez: | 9156 |
Belongs to: |
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XPG/RAD2 endonuclease family |
EXOI; exonuclease 1; Exonuclease I; HEX1rad2 nuclease family member, homolog of S. cerevisiae exonuclease 1; hExo1; hExoIEC 3.1
Mass (kDA):
94.103 kDA
Human | |
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Location: | 1q43 |
Sequence: | 1; NC_000001.11 (241847967..241889939) |
Highly expressed in bone marrow, testis and thymus. Expressed at lower levels in colon, lymph nodes, ovary, placenta, prostate, small intestine, spleen and stomach.
Nucleus. Colocalizes with PCNA to discrete nuclear foci in S-phase.
What is Steven Boster? What does the Anti-Exonuclease-1 (Exo1) Marker to the scientific community mean? Let's discuss the Biological significance and clinical applications of this marker in this Boster Bio article. Don't forget, sign up to our blog! Stay informed about the latest developments in biomedicine.
The EXO1 marker is a remnant of Steve Boster's past. Steve was a fan of southern gospel music. He would sing very low in public and in private. He also enjoyed auto racing. He rarely missed an evening race on Fridays at the local dirt track. His love for cars extended to extra-long weekend events. The EXO1 marker ultimately helped Steve to recall his life and to bring him back to the things he loved.
EXO1 belongs to the Rad2 nuclease class and has 5'-flap exonuclease activity and 5''-flap-flap endonuclease activity. It was first discovered in meiosis in yeast fission and is involved in multiple DNA metabolism pathways making it an attractive candidate for mutations during oncogenesis. Its function in the MMS2 error-free branch of the PRR pathway has been identified.
Developed by Boster Bio, the Anti-Exonuclease1 Marker is tested in ELISA, IF, and WB. The anti-Exo1 marker reacts with Human, Mouse, and PLGA three species that have different levels of expression. Researchers can submit their research to receive product credits as well as other perks, such as free samples.
Originally isolated from a screening for gene products that are involved in recombination EXO1 plays a crucial role in restarting stalled replications forks. It is also believed to be an essential part of the MMS2 error-free bypass pathway in the PRR. Exo1 mutants of rad51Dand the rad52D mutant, showed an epistatic connection to exo1D for MMS sensitivity.
It has been suggested that the anti-Exonuclease 1 (EXO1) marker is a recombinase-exonuclease-like enzyme. It is also an MMS2 hypostasis as well with other components of PRR's error-free branch. EXO1 was also discovered to be independent of MMR. In the msh2D or pms1D mutants there was no genetic connection with MMR.
The biochemical activity of EXO1 has been characterized particularly in the NH2-terminal part of the gene which is also known as HEX N2. This part of the gene encodes the active exonuclease domain. The full-length EXO1 protein was only partially studied. Studies focused mostly on biochemical activity in various pH and salt conditions. It is nevertheless important to characterize the entire protein to understand its exonucleaselytic capabilities.
Genetic and molecular studies of the EXO1 marker suggest that it plays a crucial role in single-base IDL mispairing and in mutation avoidance. It also plays a role in mitotic recombination in yeast. The role of Exo1 in MMR has been confirmed through physical interactions with MLh2 and MSH2. Mutant strains of EXO1 demonstrated synergistic mutation rates.
The mutations in EXO1 are thought to deactivate its function and increase the vulnerability of patients to tumorigenesis. In a recent study the authors found that some mice with germ-line variations of EXO1 had an increased incidence of lymphoma, and a lower survival rate. However, tumors that had EXO1 mutations did not display MSI at dinucleotide repeat markers.
EXO1 is located on chromosomes 1q42-43. It is abundantly expressed in a variety of tissues, including the colon, testis and placenta. The results of a molecular study have revealed that EXO1 is involved in mismatch repair (MMR) by interfacing with MSH2 and MSH3. While the EXO1 gene is crucial for 5'-directed DNA mismatch repair recent biochemical studies have revealed that Exo1 may also be involved in 3'-nick-directed DNA mismatch repair.
Although Exo1 is able to bind 14-3-3 protein however, its central region does not. The deletion of this central region of Exo1 enhances the binding of PCNA while inhibiting its association with 14-3-3 proteins. Further research is required to establish the precise molecular functions of Exo1 gene, including its significance in the biological world. Exo1 can phosphorylate and dephosphorylate in many ways.
The presence of Exo1 is crucial for meiosis. Mice deficient in the Exo1 gene are not able to meiosis as they lack this gene. They also are unable to produce Spermatocytes. These experiments revealed that the gene is crucial to meiosis. However, its position within a pachynema might not be sufficient to ensure stable chiasmata.
EXO1 is involved in DNA repair, plays a role in stabilization of chromatin and regulates DNA replication. EXO1 expression is affected by at most nine genetic variants. A well-known SNP could also be a biomarker for carcinogenesis. It is not easy to determine the causal role of genetic polymorphisms that are moderate due to the diversity in cancer.
Human cancer cells have shown that EXO1 expression is extremely variable. Knockdown of EXO1 knockdown has a negative effect on clonogenic cells' growth. ATM accumulation may partly regulate EXO1-related radiosensitivity. EXO1 knockdown can reduce G2/M-associated arrest of HCC cells while silencing EXO1 leads to higher levels of gH2Ax loci. These results contradict previous reports that EXO1 knockdown did not affect HCC cells in their growth or survival under IR.
The EXO1 gene is part of the RAD2 nuclease familia. It encodes an 846 amino acid protein. It is composed of an N-terminal nuclease domain as well as several interaction domains. Other proteins, for instance, the mismatch repair protein MLh2 or MSH2 are essential for the exonuclease enzyme activity.
In the Oncomine database, EXO1 mRNA expression was measured in samples of HCC and adjacent normal liver tissues. The QuantiGene Plex 2.0 analyzer was used to analyze the data. Additionally, EXO1 mRNA expression was significantly elevated in the HCC tumors of 124 samples, while the expression level was equal in two non-tumorous tissues. Furthermore it was found that the EXO1 gene is highly expressed in non-tumor liver tissues.
The Exo1 gene is a transcription factor found in the Golgi apparatus , which controls the tubules. Exo1 is also essential for the exchange of fatty acids activity of Bars50 in the Golgi and ARF1 inside the Golgi. It can distinguish between the two. Its expression in the ER could also influence the function of ARF-GEF. There are many biological and clinical applications for the EXO1 gene.
Exo1 is a transcriptional factor that regulates the synthesis of g-H2AX and ATM. The knockdown of the gene is a highly sensitive marker for cancer. Exo1 also has the capability to boost clonogenic survival cancer cells. The knockdown of Exo1 causes ATM accumulation and the formation of G-H2AX-related loci. These proteins were found in tumor cells via Western blots. Statistical significance was determined by the Student's t test.
PMID: 9788596 by Schmutte C., et al. Human exonuclease I interacts with the mismatch repair protein hMSH2.
PMID: 9823303 by Tishkoff D.X., et al. Identification of a human gene encoding a homologue of Saccharomyces cerevisiae EXO1, an exonuclease implicated in mismatch repair and recombination.