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Epigenetic DNA modification N6-methyladenine inhibits DNA replication by Sulfolobus solfataricus Y-family DNA polymerase Dpo4.
- Source :
-
Archives of Biochemistry & Biophysics . Oct2019, Vol. 675, pN.PAG-N.PAG. 1p. - Publication Year :
- 2019
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00039861
- Volume :
- 675
- Database :
- Academic Search Index
- Journal :
- Archives of Biochemistry & Biophysics
- Publication Type :
- Academic Journal
- Accession number :
- 139074575
- Full Text :
- https://doi.org/10.1016/j.abb.2019.108120