What is the role of FEN1 in DNA replication?
FEN1 maintains stable telomeres by facilitating replication through the G-rich lagging strand telomere, thereby ensuring high fidelity telomere replication.
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.
In which process is the enzyme FEN1 involved?
Substrate specificity allows FEN1 to process intermediates of Okazaki fragment maturation, long-patch base excision repair, telomere maintenance, and stalled replication fork rescue. For Okazaki fragments, the RNA primer is displaced into a 5′ flap and then cleaved off.
Is FEN1 an exonuclease?
The conserved FEN-1 C terminus binds proliferating cell nuclear antigen (PCNA) and positions FEN-1 to act primarily as an exonuclease in DNA replication, in contrast to its endonuclease activity in DNA repair.
What would happen without topoisomerase?
Topoisomerase alleviates supercoiling downstream of the origin of replication. In the absence of topoisomerase, supercoiling tension would increase to the point where DNA could fragment. DNA replication could not be initiated because there would be no RNA primer. DNA strands would not be ligated together.
What is the use of topoisomerase?
Topoisomerase: A class of enzymes that alter the supercoiling of double-stranded DNA. (In supercoiling the DNA molecule coils up like a telephone cord, which shortens the molecule.) The topoisomerases act by transiently cutting one or both strands of the DNA.
How does flap endonuclease work?
Flap endonuclease 1 (FEN1) substrate recognition and cleavage. FEN1 (a) recognizes the displaced flap, (b) binds to the base of the flap, (c) bends the substrate into a 100° angle to arrange the one-nucleotide 3′ overhang and 5′ displaced flap in the active site, and (d) precisely cleaves the flap, generating a nick.
Why is topoisomerase necessary?
Topoisomerases catalyze and guide the unknotting or unlinking of DNA by creating transient breaks in the DNA using a conserved tyrosine as the catalytic residue. The insertion of (viral) DNA into chromosomes and other forms of recombination can also require the action of topoisomerases.
