FEN1

Official Full Name

flap structure-specific endonuclease 1

Organism

Homo sapiens

Gene ID

2237

Background

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. [provided by RefSeq, Jul 2008]

Synonyms

MF1; RAD2; FEN-1

Cat.No.	Product Name	Price
CSC-DC005669	Panoply™ Human FEN1 Knockdown Stable Cell Line	Inquiry
CSC-RK0270	Human FEN1 Knockdown Cell Line-HeLa	Inquiry
CSC-SC005669	Panoply™ Human FEN1 Over-expressing Stable Cell Line	Inquiry

Cat.No.	Product Name	Price
AD06178Z	Human FEN1 adenoviral particles	Inquiry
LV12788L	human FEN1 (NM_004111) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH294037	shRNA set against Mouse FEN1 (NM_007999.4)	Inquiry
SHH294041	shRNA set against Rat FEN1 (NM_053430.1)	Inquiry
SHW002472	shRNA set against Chicken FEN1 (NM_001079491)	Inquiry
SHW015740	shRNA set against Danio rerio FEN1 (NM_198820)	Inquiry

Cat.No.	Product Name	Price
CDCB177215	Danio rerio FEN1 ORF Clone (NM_198820)	Inquiry
CDCB186119	Rabbit FEN1 ORF clone (XM_008274406.1)	Inquiry
CDCS411613	Human FEN1 ORF Clone (BC000323)	Inquiry
CDFG022325	Mouse Fen1 cDNA Clone(BC010203)	Inquiry
CDFR013173	Rat Fen1 cDNA Clone(NM_053430.1)	Inquiry
MiUTR1R-01868	FEN1 miRNA 3'UTR clone	Inquiry
MiUTR3H-03334	FEN1 miRNA 3'UTR clone	Inquiry
CDCB163947	Chicken FEN1 ORF Clone (NM_001079491)	Inquiry
CDCG003706	Mouse FEN1 ORF clone(NM_007999.4)	Inquiry
CDCR380260	Rat Fen1 ORF Clone(NM_053430.1)	Inquiry

Detailed Information

FEN1 is highly expressed in a variety of cancer cells and is closely related to the occurrence and development of cancer. The up-regulation of certain DNA repair elements in cancer cells is one of the important reasons for resistance and resistance to chemotherapy and radiotherapy strategies, and is a bottleneck in cancer treatment. In recent years, the mechanism of FEN1 has been gradually revealed, and its significance in the development of anti-tumor strategies has gradually received attention. FEN1 is a structure-specific enzyme that can recognize and cleave three-base overlapping structures (triple nucleic acids), release 5'-flap fragments, and has a highly efficient and stable cutting efficiency. Based on this feature, through different signal output methods, FEN1 enzyme is now used in DNA, RNA, virus and other amplification detection.

Figure 1. A model of methylation-based regulation of hFEN. ( Xu, H., et al. 2018)

Biological Functions of FEN1

FEN1 can specifically remove the 5'-end single-stranded DNA or RNA produced during the DNA strand displacement synthesis process catalyzed by DNA polymerase. FEN1 is a structure-specific nuclease that requires divalent metal ions to play a catalytic role. FEN1 is an essential enzyme in eukaryotic lagging-strand DNA replication, long-patch base excision repair (LP-BER) and nucleotide excision repair (nucleotide excision repair, NER). In addition, FEN1 also plays an important role in maintaining telomere stability, restarting stalled replication forks, DNA fragmentation, and processing trinucleotide repeat expansion (TRN). Studies have shown that FEN1 mainly has the functions of maintaining telomere stability, performing base and nucleotide excision repair, and promoting the maturation of Okazaki fragments. In DNA replication and repair, FEN1 interacts with PCNA (proliferating cell nuclear antigen) to form a "sliding clip", which then completes the task of nucleic acid cutting.

The Role of FEN1 in Cancer

There are many reports on the correlation between FEN1 and tumors: (1) It is highly expressed in prostate cancer, pancreatic cancer, gastric cancer, lung cancer, neuroblastoma and other tumor cells; (2) It can be used as a biomarker for breast cancer, ovarian cancer, gastric cancer and other tumors, and can increase the susceptibility of lung cancer and gastrointestinal cancer; (3) The high expression of FEN1 is closely related to the low survival rate of tumor patients, and it is also positively related to the poor prognosis of prostate cancer patients undergoing prostatectomy; (4) Knockdown of FEN1 can inhibit human colorectal cancer cells with RAD54B mutation, inhibit the growth of human prostate cancer cells, and sensitize trastuzumab, and enhance the sensitivity of glioma cells to temozolomide and cisplatin; (5) Paclitaxel combined with FEN1 inhibitor has a synergistic anti-tumor effect on cervical cancer cells. Therefore, inhibition of FEN1 can inhibit tumor cells.

Mutations or silencing of DNA damage response (DDR) genes are common in tumor cells. Studies have found that FEN1 and many cancer-related genes in the human body such as RAD54B, CDC4, MRE11A, RNF20 and SMC3 constitute a synthetic lethal partner. Among them, RAD54B is a gene that mutates during the process of somatic cell mutations into cancer cells, and has the effect of affecting chromosome stability. CDC4 is a gene mutated in a variety of tumors (such as prostate cancer, pancreatic cancer, and colorectal cancer). RNF20, SMC3 and MRE11A are highly mutated genes in colorectal cancer. Studies have shown that FEN1 can interact with a variety of proteins in cells to control the formation of a signal network, which provides the possibility for the synthesis of lethal strategies. In fact, FEN1 is considered to be a possible synthetic lethal partner with multiple important genes in the DDR pathway, and mutations in these genes can occur in many different tumors.

References:

Xu, H., Shi, R., Han, W., Cheng, J., Xu, X., Cheng, K., & Zhao, Y. (2018). Structural basis of 5' flap recognition and protein-protein interactions of human flap endonuclease 1. Nucleic Acids Research, 46(21), 11315-11325.
Shammas, M. A., Buon, L., Kumar, S., Samur, M. K., Alagpulinsa, D., Nanjappa, P., & Munshi, N. C. (2016). Flap Structure-Specific Endonuclease 1 (FEN1) May be a Key Mediator of Genome Instability in Myeloma: A Cellular Vulnerability with Potential Therapeutic Significance. Blood, 128(22), 4440-4440.
Xu, S., Cao, S., Zou, B., Yue, Y., Gu, C., Chen, X., & Zhou, G. (2016). An alternative novel tool for DNA editing without target sequence limitation: the structure-guided nuclease. Genome Biology, 17(1), 186-186.

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