Topological impact of noncanonical DNA structures on Klenow fragment of DNA polymerase.

Abstract:

:Noncanonical DNA structures that stall DNA replication can cause errors in genomic DNA. Here, we investigated how the noncanonical structures formed by sequences in genes associated with a number of diseases impacted DNA polymerization by the Klenow fragment of DNA polymerase. Replication of a DNA sequence forming an i-motif from a telomere, hypoxia-induced transcription factor, and an insulin-linked polymorphic region was effectively inhibited. On the other hand, replication of a mixed-type G-quadruplex (G4) from a telomere was less inhibited than that of the antiparallel type or parallel type. Interestingly, the i-motif was a better inhibitor of replication than were mixed-type G4s or hairpin structures, even though all had similar thermodynamic stabilities. These results indicate that both the stability and topology of structures formed in DNA templates impact the processivity of a DNA polymerase. This suggests that i-motif formation may trigger genomic instability by stalling the replication of DNA, causing intractable diseases.

authors

Takahashi S,Brazier JA,Sugimoto N

doi

10.1073/pnas.1704258114

subject

Has Abstract

pub_date

2017-09-05 00:00:00

pages

9605-9610

issue

36

eissn

0027-8424

issn

1091-6490

pii

1704258114

journal_volume

114

pub_type

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