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Title: Structures of the Catalytic Domain of Bacterial Primase DnaG in Complexes with DNA Provide Insight into Key Priming Events

Abstract

Bacterial primase DnaG is an essential nucleic acid polymerase that generates primers for replication of chromosomal DNA. The mechanism of DnaG remains unclear due to the paucity of structural information on DnaG in complexes with other replisome components. Furthermore we report the first crystal structures of noncovalent DnaG–DNA complexes, obtained with the RNA polymerase domain of Mycobacterium tuberculosis DnaG and various DNA ligands. One structure, obtained with ds DNA, reveals interactions with DnaG as it slides on ds DNA and suggests how DnaG binds template for primer synthesis. In another structure, DNA in the active site of DnaG mimics the primer, providing insight into mechanisms for the nucleotide transfer and DNA translocation. In conjunction with the recent cryo-EM structure of the bacteriophage T7 replisome, this study yields a model for primer elongation and hand-off to DNA polymerase.

Authors:
 [1];  [2]; ORCiD logo [1]
  1. Univ. of Kentucky, Lexington, KY (United States)
  2. Univ. of California, San Diego, La Jolla, CA (United States)
Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Org.:
SER-CAT
OSTI Identifier:
1438848
Resource Type:
Accepted Manuscript
Journal Name:
Biochemistry
Additional Journal Information:
Journal Volume: 57; Journal Issue: 14; Journal ID: ISSN 0006-2960
Publisher:
American Chemical Society (ACS)
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; anions; peptides and proteins; genetics; crystal structure; ions; DNA replication; replisome; DNA binding; tuberculosis

Citation Formats

Hou, Caixia, Biswas, Tapan, and Tsodikov, Oleg V. Structures of the Catalytic Domain of Bacterial Primase DnaG in Complexes with DNA Provide Insight into Key Priming Events. United States: N. p., 2018. Web. doi:10.1021/acs.biochem.8b00036.
Hou, Caixia, Biswas, Tapan, & Tsodikov, Oleg V. Structures of the Catalytic Domain of Bacterial Primase DnaG in Complexes with DNA Provide Insight into Key Priming Events. United States. https://doi.org/10.1021/acs.biochem.8b00036
Hou, Caixia, Biswas, Tapan, and Tsodikov, Oleg V. Tue . "Structures of the Catalytic Domain of Bacterial Primase DnaG in Complexes with DNA Provide Insight into Key Priming Events". United States. https://doi.org/10.1021/acs.biochem.8b00036. https://www.osti.gov/servlets/purl/1438848.
@article{osti_1438848,
title = {Structures of the Catalytic Domain of Bacterial Primase DnaG in Complexes with DNA Provide Insight into Key Priming Events},
author = {Hou, Caixia and Biswas, Tapan and Tsodikov, Oleg V.},
abstractNote = {Bacterial primase DnaG is an essential nucleic acid polymerase that generates primers for replication of chromosomal DNA. The mechanism of DnaG remains unclear due to the paucity of structural information on DnaG in complexes with other replisome components. Furthermore we report the first crystal structures of noncovalent DnaG–DNA complexes, obtained with the RNA polymerase domain of Mycobacterium tuberculosis DnaG and various DNA ligands. One structure, obtained with ds DNA, reveals interactions with DnaG as it slides on ds DNA and suggests how DnaG binds template for primer synthesis. In another structure, DNA in the active site of DnaG mimics the primer, providing insight into mechanisms for the nucleotide transfer and DNA translocation. In conjunction with the recent cryo-EM structure of the bacteriophage T7 replisome, this study yields a model for primer elongation and hand-off to DNA polymerase.},
doi = {10.1021/acs.biochem.8b00036},
journal = {Biochemistry},
number = 14,
volume = 57,
place = {United States},
year = {2018},
month = {3}
}

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Works referencing / citing this record:

A structural view of bacterial DNA replication
journal, April 2019


DnaG Primase—A Target for the Development of Novel Antibacterial Agents
journal, August 2018