DNA Polymerase Delta Exhibits Altered Catalytic Properties on Lysine Acetylation

DNA polymerase delta is the primary polymerase that is involved in undamaged nuclear lagging strand DNA replication. Our mass-spectroscopic analysis has revealed that the human DNA polymerase δ is acetylated on subunits p125, p68, and p12. Using substrates that simulate Okazaki fragment intermediate...

Full description

Saved in:
Bibliographic Details
Published in:Genes 2023-03, Vol.14 (4), p.774
Main Authors: Njeri, Catherine, Pepenella, Sharon, Battapadi, Tripthi, Bambara, Robert A, Balakrishnan, Lata
Format: Article
Language:English
Subjects:
Acetylation
Annealing
Catalysis
Deoxyribonucleic acid
DNA
DNA - genetics
DNA - metabolism
DNA biosynthesis
DNA damage
DNA polymerase
DNA Polymerase III - genetics
DNA Polymerase III - metabolism
DNA polymerases
DNA Replication
DNA-directed DNA polymerase
Efficiency
Enzymes
Genetic research
Genomes
Humans
Intermediates
Kinases
Lysine
Lysine - genetics
Phosphorylation
Physiological aspects
Proteins
Replication
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:DNA polymerase delta is the primary polymerase that is involved in undamaged nuclear lagging strand DNA replication. Our mass-spectroscopic analysis has revealed that the human DNA polymerase δ is acetylated on subunits p125, p68, and p12. Using substrates that simulate Okazaki fragment intermediates, we studied alterations in the catalytic properties of acetylated polymerase and compared it to the unmodified form. The current data show that the acetylated form of human pol δ displays a higher polymerization activity compared to the unmodified form of the enzyme. Additionally, acetylation enhances the ability of the polymerase to resolve complex structures such as G-quadruplexes and other secondary structures that might be present on the template strand. More importantly, the ability of pol δ to displace a downstream DNA fragment is enhanced upon acetylation. Our current results suggest that acetylation has a profound effect on the activity of pol δ and supports the hypothesis that acetylation may promote higher-fidelity DNA replication.
ISSN:2073-4425
2073-4425
DOI:10.3390/genes14040774