DNA and Chromosomes
The nature of the DNA substrate influences pre-catalytic conformational changes of DNA polymerase β
DNA polymerase β (Pol β) is essential for maintaining genomic integrity. During short-patch base excision repair (BER), Pol β incorporates a nucleotide into a single-gapped DNA substrate. Pol β may also function in long-patch BER, where the DNA substrate consists of larger gap sizes or 5′-modified downstream DNA. We have recently shown that Pol β fills small gaps in DNA during microhomology-mediated end-joining as part of a process that increases genomic diversity. Our previous results with single-nucleotide gapped DNA show that Pol β undergoes two pre-catalytic conformational changes upon binding to the correct nucleotide substrate.Rate-determining Step of Flap Endonuclease 1 (FEN1) Reflects a Kinetic Bias against Long Flaps and Trinucleotide Repeat Sequences
Background: FEN1 removes 5′-flaps during DNA replication and repair.Results: With increasing flap length, rate of removal decreases, and the rate-determining step changes. Trinucleotide repeat (TNR) flaps are removed slower than mixed sequence flaps of the same length.Conclusion: FEN1 is biased against long flaps and TNR sequences.Significance: These results provide a kinetic perspective on the role of FEN1 in DNA replication and repair.
