What is FEN1 in DNA replication?
Flap endonuclease (FEN-1) removes 5′ overhanging flaps in DNA repair and processes the 5′ ends of Okazaki fragments in lagging strand DNA synthesis.
Is FEN1 an exonuclease?
Human FEN1, a metallonuclease, is composed of a nuclease domain [made up of N-terminal (N), intermediate (I), and C-terminal (C) sections] and an extended C-terminal region, which is responsible for important interactions with proteins including PCNA and the Werner protein (WRN) (44, 47–49).
What do flap endonuclease do?
Flap endonucleases (FENs, also known as 5′ nucleases in older references) are a class of nucleolytic enzymes that act as both 5′-3′ exonucleases and structure-specific endonucleases on specialised DNA structures that occur during the biological processes of DNA replication, DNA repair, and DNA recombination.
What are DNA flaps?
DNA flaps function as intermediates in DNA metabolism. 3′-Flaps are generated as intermediates for homologous recombination. 5′-flaps, on the other hand, arise as necessary but dangerous DNA structures during DNA replication and DNA damage response.
Is FEN1 an enzyme?
FEN1 is an essential enzyme in an inaccurate pathway for repair of double-strand breaks in DNA called microhomology-dependent alternative end joining or microhomology-mediated end joining (MMEJ). MMEJ always involves at least a small deletion, so that it is a mutagenic pathway.
Are topoisomerases endonucleases?
Topoisomerases are isomerase enzymes that act on the topology of DNA….Topoisomerase.
| DNA Topoisomerase, ATP-dependent (type II) | |
|---|---|
| Identifiers | |
| EC no. | 5.6.2.2 |
| Databases | |
| IntEnz | IntEnz view |
How do exonucleases work?
Exonucleases are enzymes that work by cleaving nucleotides one at a time from the end (exo) of a polynucleotide chain. Its close relative is the endonuclease, which cleaves phosphodiester bonds in the middle (endo) of a polynucleotide chain.
Does topoisomerase rejoin DNA?
After cutting and relaxing (or untangling/unknotting) DNA, topoisomerases quickly rejoin the DNA backbone. If left unrepaired, breaks in the DNA can be lethal to cells.
What is the function of FEN1 in breast cancer?
Endonuclease FEN1 Coregulates ERalpha Activity and Provides a Novel Drug Interface in Tamoxifen-Resistant Breast Cancer. FEN1 endonuclease as a therapeutic target for human cancers with defects in homologous recombination.
What does FEN1 stand for?
Inhibition of one of these targets, flap endonuclease 1 (FEN1), with small-molecule inhibitors or siRNA knockdown of FEN1 expression preferentially killed BRCA1 and BRCA2 mutant cancer cell lines as well as some additional cancer cell lines without BRCA1 or BRCA2 defects.
How does Fanconi anemia affect FEN1?
The FEN1 E359K germline mutation disrupts the FEN1-WRN interaction and FEN1 GEN activity, causing aneuploidy-associated cancers. Human Fanconi anemia complementation group a protein stimulates the 5′ flap endonuclease activity of FEN1.
Is Fanconi anemia a biomarker for ovarian cancer?
FEN1 is a promising biomarker in breast and ovarian epithelial cancer. The FEN1 E359K germline mutation disrupts the FEN1-WRN interaction and FEN1 GEN activity, causing aneuploidy-associated cancers. Human Fanconi anemia complementation group a protein stimulates the 5′ flap endonuclease activity of FEN1.