Insights into eukaryotic DNA priming from the structure and functional interactions of the 4Fe-4S cluster domain of human DNA primase.

Proceedings of the National Academy of Sciences of the United States of America
Sivaraja VaithiyalingamWalter J Chazin

Abstract

DNA replication requires priming of DNA templates by enzymes known as primases. Although DNA primase structures are available from archaea and bacteria, the mechanism of DNA priming in higher eukaryotes remains poorly understood in large part due to the absence of the structure of the unique, highly conserved C-terminal regulatory domain of the large subunit (p58C). Here, we present the structure of this domain determined to 1.7-A resolution by X-ray crystallography. The p58C structure reveals a novel arrangement of an evolutionarily conserved 4Fe-4S cluster buried deeply within the protein core and is not similar to any known protein structure. Analysis of the binding of DNA to p58C by fluorescence anisotropy measurements revealed a strong preference for ss/dsDNA junction substrates. This approach was combined with site-directed mutagenesis to confirm that the binding of DNA occurs to a distinctively basic surface on p58C. A specific interaction of p58C with the C-terminal domain of the intermediate subunit of replication protein A (RPA32C) was identified and characterized by isothermal titration calorimetry and NMR. Restraints from NMR experiments were used to drive computational docking of the two domains and generate a mode...Continue Reading

References

Sep 5, 1993·Journal of Molecular Biology·L Holm, C Sander
Nov 21, 2000·Trends in Biochemical Sciences·B Arezi, R D Kuchta
Jan 3, 2001·Nature Structural Biology·J L Keck, J M Berger
Jun 8, 2001·Annual Review of Biochemistry·D N Frick, C C Richardson
Jan 20, 2004·Nature Structural & Molecular Biology·Georg LippsPatrick Cramer
Mar 29, 2005·Nature Structural & Molecular Biology·Alphonse I ArunkumarWalter J Chazin
Apr 7, 2005·Current Opinion in Chemical Biology·Olga A Lukianova, Sheila S David
Apr 9, 2005·Critical Reviews in Biochemistry and Molecular Biology·Parie Garg, Peter M J Burgers
Nov 8, 2005·Nature Structural & Molecular Biology·Si-Houy Lao-SirieixLuca Pellegrini
Aug 29, 2006·Nucleic Acids Research·Ellen FanningAndrew R Nager
Aug 21, 2007·Nature Structural & Molecular Biology·Sebastian KlingeLuca Pellegrini
Sep 26, 2007·The Journal of Biological Chemistry·Brian E WeinerWalter J Chazin
Jan 15, 2008·Nature Structural & Molecular Biology·Jacob E CornJames M Berger
Apr 30, 2008·Nucleic Acids Research·Sergey Lyskov, Jeffrey J Gray
Jun 23, 2009·Biochimica Et Biophysica Acta·Robert D Kuchta, Gudrun Stengel
Jan 6, 2010·Journal of the American Chemical Society·Joseph C GenereuxJacqueline K Barton

❮ Previous
Next ❯

Citations

Sep 24, 2011·Journal of the American Chemical Society·Timothy P MuiJacqueline K Barton
Aug 1, 2013·Journal of the American Chemical Society·Catrina G PheeneyJacqueline K Barton
Sep 18, 2013·Proceedings of the National Academy of Sciences of the United States of America·Mairi Louise KilkennyLuca Pellegrini
Jul 1, 2011·Nucleic Acids Research·Rafael Núñez-RamírezOscar Llorca
Jan 31, 2012·Nucleic Acids Research·Yuliang Wu, Robert M Brosh
Jan 11, 2013·Nucleic Acids Research·Chris A BroseyWalter J Chazin
Mar 19, 2014·Acta Crystallographica. Section F, Structural Biology Communications·Andrey G BaranovskiyTahir H Tahirov
Jan 22, 2014·Nucleic Acids Research·Sukhvinder GillPatrick Forterre
Dec 30, 2014·Progress in Biophysics and Molecular Biology·Norie Sugitani, Walter J Chazin
Dec 16, 2011·Current Opinion in Structural Biology·Malcolm F White, Mark S Dillingham
Dec 6, 2011·Gene·Rutt LilleojaSulev Kõks
May 20, 2015·Computational and Structural Biotechnology Journal·Julien BoudetGeorg Lipps
Feb 7, 2015·Biochimica Et Biophysica Acta·Jill O FussJohn A Tainer
Jan 15, 2015·Biochimica Et Biophysica Acta·Viktoria Désirée Paul, Roland Lill
Jan 4, 2012·Journal of Molecular Recognition : JMR·Rajesh GhaiBrett M Collins
Oct 12, 2012·Environmental and Molecular Mutagenesis·Irina S-R WaisertreigerYouri I Pavlov
May 15, 2015·Protein Science : a Publication of the Protein Society·Wenlin LiNick V Grishin
Nov 19, 2013·Journal of Molecular Biology·Sivaraja VaithiyalingamWalter J Chazin
Mar 14, 2013·Trends in Cell Biology·Stefan Westermann, Alexander Schleiffer
Feb 18, 2017·Genes·Andrey G Baranovskiy, Tahir H Tahirov
Nov 24, 2017·Nature Communications·Sandro HolzerLuca Pellegrini
Nov 14, 2019·Cellular and Molecular Life Sciences : CMLS·Nicole M HoitsmaBret D Freudenthal
Mar 16, 2016·The Journal of Biological Chemistry·Andrey G BaranovskiyTahir H Tahirov
Sep 19, 2019·Metallomics : Integrated Biometal Science·Paul A Lindahl
Jan 1, 2015·The Journal of Biological Chemistry·Andrey G BaranovskiyTahir H Tahirov
Dec 14, 2018·Proceedings of the National Academy of Sciences of the United States of America·Elizabeth O'BrienJacqueline K Barton
Jun 22, 2019·Annual Review of Biochemistry·Jacqueline K BartonElizabeth O'Brien
Aug 19, 2014·Protein Science : a Publication of the Protein Society·Basudeb Bhattacharyya, James L Keck
Dec 30, 2015·The Journal of Biological Chemistry·Andrey G BaranovskiyTahir H Tahirov
Jan 11, 2021·The Plant Journal : for Cell and Molecular Biology·Jonathan Przybyla-ToscanoOlivier Keech
May 30, 2020·Journal of the American Chemical Society·Rebekah M B SilvaJacqueline K Barton
Nov 16, 2018·Journal of the American Chemical Society·Elizabeth O'BrienJacqueline K Barton

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.