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Browsing by Subject "Okazaki fragment maturation"

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    DNA Polymerase Delta Exhibits Altered Catalytic Properties on Lysine Acetylation
    (MDPI, 2023-03-23) Njeri, Catherine; Pepenella, Sharon; Battapadi, Tripthi; Bambara, Robert A.; Balakrishnan, Lata; Biology, School of Science
    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.
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