当前位置： SCI文献检索 > ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS期刊下所有文献 > Epigenetic DNA modification N6-methyladenine inhibits DNA replication by Sulfolobus solfataricus Y-family DNA polymerase Dpo4.

Epigenetic DNA modification N6-methyladenine inhibits DNA replication by Sulfolobus solfataricus Y-family DNA polymerase Dpo4.

Abstract：

:Dpo4 is a representative model of Y-family DNA polymerase and is therefore one of the most intensively studied DNA polymerase. 6 mA, an epigenetic marker, plays important roles in regulation of various biological processes. However, its effects on DNA replication by Dpo4 is completely unknown. Here, we found that 6 mA and its intermediate Hyp inhibits primer extension by Dpo4, showing an obvious blockage just one nucleotide before 6 mA or Hyp. 6 mA reduces dTTP incorporation efficiency, next-base extension efficiency, binding affinity of DNA to Dpo4, binding affinity of dTTP to Dpo4-DNA complex, the fraction of productive Dpo4 or productive ternary complex, and the burst incorporation rate, explaining the inhibition effects of 6 mA on DNA replication by Dpo4. Hyp is similar to G and dCTP is preferentially incorporated opposite Hyp by Dpo4, resulting in A:T to G:C mutation. Relative to dTTP incorporation opposite unmodified A, Hyp reduces dCTP incorporation efficiency, next-base extension efficiency, the priority in extension beyond correct pair, binding affinity of Dpo4 to DNA, binding of dCTP to Dpo4-DNA complex, and the burst incorporation efficiency, explaining the inhibition effects of Hyp on DNA replication by Dpo4. This work provides insight in the effects of epigenetically modified 6 mA and Hyp on DNA replication by a representative Y-family DNA polymerase Dpo4.

journal_name

Arch Biochem Biophys

journal_title

Archives of biochemistry and biophysics

authors

Du K,Zhang S,Chen W,Dai M,Xu Z,Liang T,Huang W,Ling Y,Zhang H

doi

10.1016/j.abb.2019.108120

subject

Has Abstract

pub_date

2019-10-30 00:00:00

pages

108120

eissn

0003-9861

issn

1096-0384

pii

S0003-9861(19)30653-8

journal_volume

675

pub_type

杂志文章

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