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Title: Capture of a third Mg2+ is essential for catalyzing DNA synthesis

Journal Article · · Science
 [1];  [1]
  1. National Institutes of Health, Bethesda, MD (United States)

DNA polymerase is an enzyme that uses existing DNA as a template to build new DNA by adding new nucleotides to the end of the newly forming daughter strand. The enzyme mechanism that catalyzes formation of a phosphodiester bond is known to require two Mg2+ ions, and recent crystal structures have shown that a third metal ion is present after bond formation. Gao et al. used time-resolved crystallography to visualize bond formation. The enzyme-substrate complex captures a third cation before bond formation occurs, and DNA synthesis cannot occur without the third metal ion. Binding of this metal ion requires thermal motion of the enzyme-substrate complex, so that catalysis is achieved by acquiring a transient cofactor.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
DK036146–08
OSTI ID:
1259887
Journal Information:
Science, Vol. 352, Issue 6291; ISSN 0036-8075
Publisher:
AAASCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 124 works
Citation information provided by
Web of Science

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Cited By (29)

Synthesis of Selenium‐Triphosphates (dNTPαSe) for More Specific DNA Polymerization journal April 2019
Synthesis of Selenium‐Triphosphates (dNTPαSe) for More Specific DNA Polymerization journal June 2019
Crystallographic evidence for two‐metal‐ion catalysis in human pol η journal December 2018
Catalytic mechanism of DNA polymerases—Two metal ions or three? journal December 2018
Phosphate steering by Flap Endonuclease 1 promotes 5′-flap specificity and incision to prevent genome instability journal June 2017
Time-lapse crystallography snapshots of a double-strand break repair polymerase in action journal August 2017
Mechanism of error-free replication across benzo[a]pyrene stereoisomers by Rev1 DNA polymerase journal October 2017
Dynamic coordination of two-metal-ions orchestrates λ-exonuclease catalysis journal October 2018
Cation trafficking propels RNA hydrolysis journal August 2018
2.0 Å resolution crystal structure of human polκ reveals a new catalytic function of N-clasp in DNA replication journal October 2018
Intrinsic cleavage of RNA polymerase II adopts a nucleobase-independent mechanism assisted by transcript phosphate journal February 2019
Bypassing a 8,5′-cyclo-2′-deoxyadenosine lesion by human DNA polymerase η at atomic resolution journal October 2018
Extensive free-energy simulations identify water as the base in nucleotide addition by DNA polymerase journal November 2019
Characterization of six recombinant human RNase H2 bearing Aicardi-Goutiéres syndrome causing mutations journal September 2019
Calcium-driven DNA synthesis by a high-fidelity DNA polymerase journal October 2017
Pyrophosphate hydrolysis is an intrinsic and critical step of the DNA synthesis reaction journal May 2018
Crystal structures of a natural DNA polymerase that functions as an XNA reverse transcriptase journal June 2019
DNA processing by the MOBH family relaxase TraI encoded within the gonococcal genetic island journal July 2019
Structural characterization of Class 2 OLD family nucleases supports a two-metal catalysis mechanism for cleavage journal August 2019
Molecular Dynamics Analysis of Mg 2+ -dependent Cleavage of a Pistol Ribozyme Reveals a Fail-safe Secondary Ion for Catalysis journal August 2019
The Role of 3′ to 5′ Reverse RNA Polymerization in tRNA Fidelity and Repair journal March 2019
Magnesium Is a Key Player in Neuronal Maturation and Neuropathology journal July 2019
Insights into DNA polymerase δ’s mechanism for accurate DNA replication journal February 2019
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Crystallographic observation of nonenzymatic RNA primer extension posted_content March 2018
Molecular dynamics analysis of Mg 2+ ‐dependent cleavage of a pistol ribozyme reveals a fail‐safe secondary ion for catalysis journal February 2020
A new paradigm of DNA synthesis: three-metal-ion catalysis journal September 2016
Reading and Misreading 8-oxoguanine, a Paradigmatic Ambiguous Nucleobase journal May 2019
Modulation of RNA primer formation by Mn(II)-substituted T7 DNA primase journal July 2017

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