At5g26680 role in mediating transcriptional gene silencing as well as maintaining genome stability
Data show that shade avoidance 6 (SAV6; At5g26680), encodes flap endonuclease-1 (FEN1), assures proper root development through maintenance of genome integrity.
Kinetic measurements showed that the active site mutants A159V and E160D reduce the rates of hydrolysis under multiple- and single-turnover conditions on all substrates. Consistent with their dominant negative effects in heterozygotes, neither mutation affects the adoption of the substrate duplex arms in the bent conformation on the enzyme surface, although decreases in substrate binding affinity are observed.
These results reveal an important role of FEN1 phosphorylation to counteract oxygen-induced stress in the heart during the fetal-to-neonatal transition.
WDR4 regulates FEN1's potential DNA cleavage threat near the site of replication.
The FEN1 E359K germline mutation disrupts the FEN1-WRN interaction and FEN1 GEN activity, causing aneuploidy-associated cancers.
PARP1 is required for FEN1 recruitment to DNA repair intermediates in base excision repair.
FFAA Fen1 mutation causes defective Pcna -coordinated Okazaki fragment maturation.
A point mutation in the base excision repair gene flap endonuclease 1 causes a functional deficiency in repairing base damage, such that individuals carrying the mutation or similar mutations are predisposed to chemical-induced cancer development.
The stoichiometry of base excision repair enzymes is one critical factor underlying the tissue selectivity of somatic CAG expansion.
FEN1 localization within the mitochondrial compartment of mouse brain tissue
Haploinsufficiency leads to rapid tumor progression.
Distinct roles for two Mg2+ binding sites in the regulation of FEN-1 nuclease activities include enhancement of DNA substrate binding ability and modulation of conformational changes.
FEN1 has roles in DNA repair, as well as in DNA replication
Fen1 is induced independently in mouse embryonic fibroblasts by ultraviolet (UV-C)light
These data demonstrate the importance of the FEN-1/PCNA complex in DNA replication and in the embryonic development of mice.
Apc(1638N) Exo1 Fen1 mice survive longer (18 months)
The mutator phenotype of Fen1 results in the initiation of cancer, whereas chronic inflammation promotes the cancer progression.
Loss of Fen1 is associated with early-onset lymphoma and extensive embryonic apoptosis
hFEN1 regional conformational flexibility spanning a range of dynamic timescales is crucial to reach the catalytically relevant ensemble with substrate DNA.
The role of the beta-pin region in FEN1 protein interactions that are essential for DNA replication and repair.
A second nuclease is therefore required to remove the last ribonucleotides and we demonstrate that Flap endonuclease 1 (FEN1) can execute this function in vitro. Removal of RNA primers at OriL thus depends on a two-nuclease model, which in addition to RNase H1 requires FEN1 or a FEN1-like activity. These findings define the role of RNase H1 at OriL and help to explain the pathogenic consequences of disease causing mutatio
Identified APEX2 and FEN1 as synthetic lethal genes with both BRCA1 and BRCA2 loss of function in tumor cell lines.
hFEN1 residues with distinct roles in the catalytic mechanism, including those binding metal ions (Asp-34 and Asp-181), steering the 5'-flap through the active site and binding the scissile phosphate (Lys-93 and Arg-100), and stacking against the base 5' to the scissile phosphate (Tyr-40), all contribute to these rate-limiting conformational changes, ensuring efficient and specific cleavage of 5'-flaps.
Results show that both the FEN1 polymorphisms, c.-69G>A (rs174538) and c.4150G>T (rs4246215), failed to show any genetic association with the Fuchs' Endothelial Corneal Dystrophy (FECD) disease phenotype. Further data identified 'G' allele of the 3'UTR located FEN1 polymorphism c.4150G>T as the target for binding of hsa-miR-1236.
Phosphate steering is an unappreciated FEN1 function that enforces 5'-flap specificity and catalysis, preventing genomic instability.
Results provide evidence that FEN1 rs174538 and rs4246215 are significantly associated with Wilms tumor susceptibility.
FEN1 was an independent predictor of survival in pancreatic ductal adenocarcinoma
The FEN1 rs174538 A allele is a novel protective biomarker for endometriosis
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.
Results suggest that FEN1 polymorphisms may reduce the risk of breast cancer in Chinese women.
FEN1 is essential for prolifera- tion and cisplatin resistance of lung cancer cells.
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.
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.
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.
Overexpression of human XPG and FEN1 increases genome instability in U2OS cells
Data indicate that human cancer-associated genetic alterations in the FEN1 gene can contribute substantially to cancer development.
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.
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.
The protein encoded by this gene removes 5' overhanging flaps in DNA repair and processes the 5' ends of Okazaki fragments in lagging strand DNA synthesis. Direct physical interaction between this protein and AP endonuclease 1 during long-patch base excision repair provides coordinated loading of the proteins onto the substrate, thus passing the substrate from one enzyme to another. The protein is a member of the XPG/RAD2 endonuclease family and is one of ten proteins essential for cell-free DNA replication. DNA secondary structure can inhibit flap processing at certain trinucleotide repeats in a length-dependent manner by concealing the 5' end of the flap that is necessary for both binding and cleavage by the protein encoded by this gene. Therefore, secondary structure can deter the protective function of this protein, leading to site-specific trinucleotide expansions.
flap endonuclease 1
, Flap structure-specific endonuclease 1
, flap structure-specific endonuclease 1
, DNase IV
, maturation factor 1
, maturation factor-1
, 5' nuclease xFEN1a
, flap endonuclease 1-A
, flap structure-specific endonuclease 1-A