2015
DOI: 10.1093/mutage/gev083
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G-quadruplex DNA structures can interfere with uracil glycosylase activityin vitro

Abstract: Genome sequences that contain tandem repeats of guanine can form stable four-stranded structures known as G-quadruplex, or G4 DNA. While the molecular mechanisms are not fully defined, such guanine-rich loci are prone to mutagenesis and recombination. Various repair pathways function to reduce the potential for genome instability by correcting base damage and replication errors; however, it is not yet fully defined how well these processes function at G4 DNA. One frequent form of base damage occurs from cytidi… Show more

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Cited by 5 publications
(10 citation statements)
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“…UDG activity is modestly inhibited compared to the thymine interrupted and SCR positive controls when uracil is positioned directly 5' to G4 DNA (5'1 U) (69% compared to 91%; Figure 8A). For uracils positioned three bases away from G4 paired guanines, cleavage efficiency was identical to unstructured control ( Figure 8A), similar to previous results (Holton and Larson, 2015). Activity directly 3' to G4 DNA is mildly inhibited compared to thymine interrupted and SCR positive controls with an observed cleavage activity of 82% directly adjacent to G4 DNA, but when uracil is moved three bases away cleavage is essentially identical to unstructured controls ( Figure 8C).…”
Section: G4 Formation Creates An Inhibitory Footprint For Udg Activitsupporting
confidence: 87%
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“…UDG activity is modestly inhibited compared to the thymine interrupted and SCR positive controls when uracil is positioned directly 5' to G4 DNA (5'1 U) (69% compared to 91%; Figure 8A). For uracils positioned three bases away from G4 paired guanines, cleavage efficiency was identical to unstructured control ( Figure 8A), similar to previous results (Holton and Larson, 2015). Activity directly 3' to G4 DNA is mildly inhibited compared to thymine interrupted and SCR positive controls with an observed cleavage activity of 82% directly adjacent to G4 DNA, but when uracil is moved three bases away cleavage is essentially identical to unstructured controls ( Figure 8C).…”
Section: G4 Formation Creates An Inhibitory Footprint For Udg Activitsupporting
confidence: 87%
“…G4 DNA is known to be associated with genomic instability (Cea, et al, et al, 2015;, so it is important to define the actual molecular sources of mutagenesis at sequences near those participating in structure formation. Previous work has shown that the activity of UDG and the human homolog hUNG2 is reduced directly adjacent 5' or 3' to G4 DNA (Holton and Larson, 2015). Here I expand that analysis to clarify the footprint of enzyme inhibition around G4 DNA.…”
Section: Discussionmentioning
confidence: 67%
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