English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  Fidelity of DNA polymerases can be influenced by cation co-factors. Physiologically, Mg 2+  is used as a co-factor by HIV reverse transcriptase (RT) to perform catalysis; however, alternative cations including Mn 2+ , Co 2+ , and Zn 2+  can also support catalysis. Although Zn 2+  supports DNA synthesis, it inhibits HIV RT by significantly modifying RT catalysis. Zn 2+  is currently being investigated as a component of novel treatment options against HIV and we wanted to investigate the fidelity of RT with Zn 2+ .    Methods  We used PCR-based and plasmid-based alpha complementation assays as well as steady-state misinsertion and misincorporation assays to examine the fidelity of RT with Mn 2+ , Co 2+ , and Zn 2+ .    Results  The fidelity of DNA synthesis by HIV-1 RT was approximately 2.5 fold greater in Zn 2+  when compared to Mg 2+  at cation conditions optimized for nucleotide catalysis. Consistent with this, RT extended primers with mismatched 3′ nucleotides poorly and inserted incorrect nucleotides less efficiently using Zn 2+  than Mg 2+ . In agreement with previous literature, we observed that Mn 2+  and Co 2+  dramatically decreased the fidelity of RT at highly elevated concentrations (6 mM). However, surprisingly, the fidelity of HIV RT with Mn 2+  and Co 2+  remained similar to Mg 2+  at lower concentrations that are optimal for catalysis.    Conclusion  This study shows that Zn 2+ , at optimal extension conditions, increases the fidelity of HIV-1 RT and challenges the notion that alternative cations capable of supporting polymerase catalysis are inherently mutagenic.

Alternative divalent cations (Zn2+, Co2+, and Mn2+) are not mutagenic at conditions optimal for HIV-1 reverse transcriptase activity