Recombinant Human Flap endonuclease 1 (FEN1)

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Code CSB-EP008585HU
Size $256
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  • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
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Product Details

Purity
Greater than 85% as determined by SDS-PAGE.
Target Names
FEN1
Uniprot No.
Research Area
Epigenetics and Nuclear Signaling
Alternative Names
DNase IV; FEN-1; FEN1; FEN1_HUMAN; Flap endonuclease 1; Flap structure specific endonuclease 1; Flap structure-specific endonuclease 1; hFEN-1; hFEN1; Maturation factor 1; MF1; Rad2
Species
Homo sapiens (Human)
Source
E.coli
Expression Region
1-380aa
Target Protein Sequence
MGIQGLAKLIADVAPSAIRENDIKSYFGRKVAIDASMSIYQFLIAVRQGGDVLQNEEGETTSHLMGMFYRTIRMMENGIKPVYVFDGKPPQLKSGELAKRSERRAEAEKQLQQAQAAGAEQEVEKFTKRLVKVTKQHNDECKHLLSLMGIPYLDAPSEAEASCAALVKAGKVYAAATEDMDCLTFGSPVLMRHLTASEAKKLPIQEFHLSRILQELGLNQEQFVDLCILLGSDYCESIRGIGPKRAVDLIQKHKSIEEIVRRLDPNKYPVPENWLHKEAHQLFLEPEVLDPESVELKWSEPNEEELIKFMCGEKQFSEERIRSGVKRLSKSRQGSTQGRLDDFFKVTGSLSSAKRKEPEPKGSTKKKAKTGAAGKFKRGK
Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.
Mol. Weight
50.0 kDa
Protein Length
Full Length
Tag Info
N-terminal 10xHis-tagged and C-terminal Myc-tagged
Form
Liquid or Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
Buffer
If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol. If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Reconstitution
We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. Our default final concentration of glycerol is 50%. Customers could use it as reference.
Troubleshooting and FAQs
Storage Condition
Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
Shelf Life
The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Lead Time
3-7 business days
Notes
Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Datasheet & COA
Please contact us to get it.
Description

The region for expressing recombinant Human FEN1 contains amino acids 1-380. This FEN1 protein is expected to have a theoretical molecular weight of 50.0 kDa. Expression of this FEN1 protein is conducted in e.coli. The FEN1 gene fragment has been modified by fusing the N-terminal 10xHis tag and C-terminal Myc tag, providing convenience in detecting and purifying the recombinant FEN1 protein during the following stages.

Flap endonuclease 1 (FEN1) is a multifunctional endonuclease involved in DNA replication and repair processes. In humans, FEN1 plays a crucial role in processing DNA intermediates during Okazaki fragment maturation, long-patch base excision repair, and nucleotide excision repair. As a structure-specific nuclease, FEN1 cleaves 5' flaps, flap structures that arise during DNA synthesis. This activity is vital for maintaining genomic stability and integrity. FEN1 also participates in DNA damage response pathways, contributing to the repair of various lesions. Dysregulation of FEN1 has been associated with genomic instability and is implicated in cancer development. Understanding FEN1's functions is essential for unraveling DNA repair mechanisms and potential therapeutic targets for cancer treatment.

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Target Background

Function
Structure-specific nuclease with 5'-flap endonuclease and 5'-3' exonuclease activities involved in DNA replication and repair. During DNA replication, cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. It enters the flap from the 5'-end and then tracks to cleave the flap base, leaving a nick for ligation. Also involved in the long patch base excision repair (LP-BER) pathway, by cleaving within the apurinic/apyrimidinic (AP) site-terminated flap. Acts as a genome stabilization factor that prevents flaps from equilibrating into structurs that lead to duplications and deletions. Also possesses 5'-3' exonuclease activity on nicked or gapped double-stranded DNA, and exhibits RNase H activity. Also involved in replication and repair of rDNA and in repairing mitochondrial DNA.
Gene References into Functions
  1. Results provide evidence that FEN1 rs174538 and rs4246215 are significantly associated with Wilms tumor susceptibility. PMID: 29937070
  2. FEN1 was an independent predictor of survival in pancreatic ductal adenocarcinoma PMID: 29735403
  3. The FEN1 rs174538 A allele is a novel protective biomarker for endometriosis PMID: 29109095
  4. This study revealed that cell apoptosis dysfunction plays a key role in the pathogenesis of LN, even though the difference in FEN1 gene 61563142-61563342 between LN patients and healthy individuals was not statistically significant. PMID: 29239254
  5. Results suggest that FEN1 polymorphisms may reduce the risk of breast cancer in Chinese women. PMID: 27801669
  6. FEN1 is essential for prolifera- tion and cisplatin resistance of lung cancer cells. PMID: 28371273
  7. Our results suggest that functional polymorphism FEN1 rs174538 G>A might affect personal susceptibility to esophageal squamous cell carcinoma . This result provides a solid theoretical foundation for further clinical study using larger sample sizes. PMID: 28319330
  8. FEN1 sculpts DNA with diffusion-limited kinetics to test DNA substrate. This DNA distortion mutually 'locks' protein and DNA conformation and enables substrate verification with extreme precision. PMID: 28230529
  9. Notably, non-small cell lung cancer patients with FEN1-overexpressed cancers were prone to have poor differentiation and poor prognosis. Furthermore, knockdown of FEN1 resulted in G1/S or G2/M phase cell cycle arrest and suppressed in vitro cellular proliferation in NSCLC cancer cells. PMID: 29037854
  10. Data indicate that human cancer-associated genetic alterations in the FEN1 gene can contribute substantially to cancer development. PMID: 27270424
  11. WRN or the Bloom syndrome helicase (BLM) stimulates DNA polymerase delta progression across telomeric G-rich repeats, only WRN promotes sequential strand displacement synthesis and FEN1 cleavage. PMID: 27849570
  12. The FEN1 rs174538 A allele is a protective biomarker for childhood ALL and this association is more significant in males and in patients at onset age of 3.5 years or older. PMID: 26708601
  13. Data indicate that Flap endonuclease 1 (FEN1) single nucleotide polymorphisms and haplotypes are associated with gallbladder cancer risk. PMID: 26668074
  14. the aim of the present study was to determine the role of FEN1 in the chemosensitivity of SGC7901 cells. PMID: 26718738
  15. Binding of DNA to human FEN1 in a bent conformation occurred independently of 5'-flap accommodation and did not require active site metal ions or the presence of conserved active site residues. PMID: 26884332
  16. In this study, we found that cohesion establishment factors, like CHlR1, cooperatively stimulate endonuclease activity of hFen1 in in vivo mimic condition, including replication protein-A-coated DNA and high salt. PMID: 26032365
  17. Under DNA repair conditions, FEN1 efficiently repaired the 5'-phoshotyrosyl bond-containing SSB substrates in the presence of DNA ligase and DNA polymerase. PMID: 26581212
  18. WDR4 regulates FEN1's potential DNA cleavage threat near the site of replication. PMID: 26751069
  19. Patients with expression of both FEN1 and RAD54B were prone to have advanced nodal involvement and significantly poor prognosis. PMID: 26431531
  20. Fen1 significantly stimulated trinucleotide repeats expansion by Pol beta, but not by the related enzyme Pol lambda. PMID: 25687118
  21. YY1 is a transcription repressor of FEN1 regulating FEN1 levels in response to DNA damaging agents. PMID: 25885449
  22. EXO1 and FEN1 cleaved the substrate at the boundary between the single-stranded 5' flap and the duplex, whereas FAN1 incised it three to four nucleotides in the double-stranded region. PMID: 26221031
  23. Rate-determining step of FEN1 reflects a kinetic bias against long flaps and trinucleotide repeat sequences. PMID: 26160176
  24. FEN1 -69G>A and 4150G>T polymorphisms may be associated with cancer susceptibility in Chinese population. PMID: 25154853
  25. Because FEN1 mutations have been identified in human cancers, our findings raise the possibility that unresolved RNA:DNA hybrid structures contribute to the genomic instability associated with cancer PMID: 25922071
  26. A novel method for monitoring functional lesion-specific recruitment of repair proteins in live cells. PMID: 25879709
  27. FEN1 protein expression was evaluated in 568 oestrogen receptor (ER) negative breast cancers, 894 ER positive breast cancers and 156 ovarian epithelial cancers. FEN1 is a promising biomarker in breast and ovarian epithelial cancer. PMID: 24880630
  28. The FEN1 E359K germline mutation disrupts the FEN1-WRN interaction and FEN1 GEN activity, causing aneuploidy-associated cancers. PMID: 24608430
  29. the mutations of the FEN1 gene maybe a rare event in the development of hepatocellular carcinomas in Korean population PMID: 24164220
  30. FEN1 SNPs and haplotypes were significantly associated with breast cancer risk. The risk alleles showed decreased FEN1 mRNA expression in breast tissues. PMID: 24440783
  31. The homotrimeric proliferating cell nuclear antigen protein (PCNA) coordinates the actions of DNA polymerase, FEN1 and DNA ligase by facilitating the hand-off intermediates between each protein during Okazaki fragment maturation PMID: 22918592
  32. Conserved basic amino acids are not required for double nucleotide unpairing and appear to act cooperatively, whereas the helical cap plays an unexpected role in hFEN1-substrate rearrangement PMID: 24126913
  33. The data provides the first observations of unpaired conformations in DNA substrates bound to hFEN1 in the presence of catalytically inert active-site metal ions and define the role of amino acid residues and divalent metal ion cofactors in this process. PMID: 23975198
  34. A cryptic targeting signal creates a mitochondrial FEN1 isoform with tailed R-Loop binding properties. PMID: 23675412
  35. This study suggested that FEN1 polymorphisms and haplotypes are associated with glioma risk. PMID: 23184144
  36. We identified small-molecule inhibitors of one such target, FEN1, and showed that these compounds were able to selectively kill human cells carrying cancer-relevant mutations. PMID: 23382697
  37. These studies demonstrate a novel role for APC in the suppression of Fen1 activity in the BER pathway PMID: 22787431
  38. Cell-cycle-dependent timing of FEN1 nuclease activity is essential for cell-cycle progression and the maintenance of genome stability. PMID: 22749529
  39. The crystal structure of the complex of importin alpha with a peptide corresponding to the FEN1 nuclear localization sequence was solved. PMID: 22751659
  40. Review: identifies superfamily motifs such as the helical gateway that select for ss-dsDNA junctions and provides key biological insights into FEN1 specificity and regulation. PMID: 22244820
  41. Data show models for the ternary PCNA/FEN1/DNA and Rad9-Rad1-Hus1 (9-1-1 complex)/FEN1/DNA assemblies. PMID: 22586102
  42. Data show that among the 13 SNPs in the 3 genes, only 3 were found to be polymorphic: R196K and K277R in the DFFB gene, and S12L in the EndoG gene, and all 6 SNPs in the FEN-1 gene were entirely monoallelic. PMID: 22011247
  43. FEN1 as an important gene in human gastrointestinal oncogenesis and genetic polymorphisms in FEN1 confer susceptibility to gastrointestinal cancers. PMID: 22072618
  44. Activity of FEN1 endonuclease on nucleosome substrates is dependent upon DNA sequence but not flap orientation. PMID: 21454907
  45. Structural and functional analyses of human FEN1:DNA complexes show structure-specific, sequence-independent recognition for nicked dsDNA bent 100 degrees with unpaired 3' and 5' flaps. PMID: 21496641
  46. these results show that FEN1 and telomerase association occurs throughout the S phase, with the maximum association in the mid S phase. PMID: 21345332
  47. FEN1 10154T variant allele decreases arachidonic acid and arachidonic acid/linoleic acid in the serum phospholipids of carriers of the APOA5-1131C allele PMID: 20802161
  48. the methylated form, but not the phosphorylated form, of FEN1 strongly interacts with proliferating cell nuclear antigen (PCNA), ensuring the 'on' and 'off' timing of its reaction PMID: 20729856
  49. FEN1 and EXO1 can eliminate structures formed by trinucleotide repeats in the course of replication, relying on endonucleolytic and exonucleolytic activities, respectively. PMID: 20643645
  50. FEN1 maintains stable telomeres by facilitating replication through the G-rich lagging strand telomere, thereby ensuring high fidelity telomere replication. PMID: 20551483

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Subcellular Location
[Isoform 1]: Nucleus, nucleolus. Nucleus, nucleoplasm. Note=Resides mostly in the nucleoli and relocalizes to the nucleoplasm upon DNA damage.; [Isoform FENMIT]: Mitochondrion.
Protein Families
XPG/RAD2 endonuclease family, FEN1 subfamily
Database Links

HGNC: 3650

OMIM: 600393

KEGG: hsa:2237

STRING: 9606.ENSP00000305480

UniGene: Hs.409065

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