4e2i › Citations

Structural basis for the interaction of a hexameric replicative helicase with the regulatory subunit of human DNA polymerase α-primase.

Zhou B, Arnett DR, Yu X, Brewster A, Sowd GA, Xie CL, Vila S, Gai D, Fanning E, Chen XS
J Biol Chem 287 26854-66 (2012)
Cited: 30 times
EuropePMC logo PMID: 22700977

Abstract

DNA polymerase α-primase (Pol-prim) plays an essential role in eukaryotic DNA replication, initiating synthesis of the leading strand and of each Okazaki fragment on the lagging strand. Pol-prim is composed of a primase heterodimer that synthesizes an RNA primer, a DNA polymerase subunit that extends the primer, and a regulatory B-subunit (p68) without apparent enzymatic activity. Pol-prim is thought to interact with eukaryotic replicative helicases, forming a dynamic multiprotein assembly that displays primosome activity. At least three subunits of Pol-prim interact physically with the hexameric replicative helicase SV40 large T antigen, constituting a simple primosome that is active in vitro. However, structural understanding of these interactions and their role in viral chromatin replication in vivo remains incomplete. Here, we report the detailed large T antigen-p68 interface, as revealed in a co-crystal structure and validated by site-directed mutagenesis, and we demonstrate its functional importance in activating the SV40 primosome in cell-free reactions with purified Pol-prim, as well as in monkey cells in vivo.

Articles - 4e2i mentioned but not cited (2)

  1. Structural basis for the interaction of a hexameric replicative helicase with the regulatory subunit of human DNA polymerase α-primase. Zhou B, Arnett DR, Yu X, Brewster A, Sowd GA, Xie CL, Vila S, Gai D, Fanning E, Chen XS. J Biol Chem 287 26854-26866 (2012)
  2. The Vaccinia Virus DNA Helicase Structure from Combined Single-Particle Cryo-Electron Microscopy and AlphaFold2 Prediction. Hutin S, Ling WL, Tarbouriech N, Schoehn G, Grimm C, Fischer U, Burmeister WP. Viruses 14 2206 (2022)


Reviews citing this publication (8)

  1. The E1 proteins. Bergvall M, Melendy T, Archambault J. Virology 445 35-56 (2013)
  2. Regulation of Rad6/Rad18 Activity During DNA Damage Tolerance. Hedglin M, Benkovic SJ. Annu Rev Biophys 44 207-228 (2015)
  3. Elaborated Action of the Human Primosome. Baranovskiy AG, Tahirov TH. Genes (Basel) 8 E62 (2017)
  4. Targeting human papillomavirus genome replication for antiviral drug discovery. Archambault J, Melendy T. Antivir Ther 18 271-283 (2013)
  5. Structural Mechanisms of Hexameric Helicase Loading, Assembly, and Unwinding. Trakselis MA. F1000Res 5 F1000 Faculty Rev-111 (2016)
  6. The Biology and Clinical Features of Cutaneous Polyomaviruses. Nguyen KD, Chamseddin BH, Cockerell CJ, Wang RC. J Invest Dermatol 139 285-292 (2019)
  7. The excluded DNA strand is SEW important for hexameric helicase unwinding. Carney SM, Trakselis MA. Methods 108 79-91 (2016)
  8. Lagging Strand Initiation Processes in DNA Replication of Eukaryotes-Strings of Highly Coordinated Reactions Governed by Multiprotein Complexes. Nasheuer HP, Onwubiko NO. Genes (Basel) 14 1012 (2023)

Articles citing this publication (20)

  1. Mechanism for priming DNA synthesis by yeast DNA polymerase α. Perera RL, Torella R, Klinge S, Kilkenny ML, Maman JD, Pellegrini L. Elife 2 e00482 (2013)
  2. Mechanism of Concerted RNA-DNA Primer Synthesis by the Human Primosome. Baranovskiy AG, Babayeva ND, Zhang Y, Gu J, Suwa Y, Pavlov YI, Tahirov TH. J Biol Chem 291 10006-10020 (2016)
  3. The CDC13-STN1-TEN1 complex stimulates Pol α activity by promoting RNA priming and primase-to-polymerase switch. Lue NF, Chan J, Wright WE, Hurwitz J. Nat Commun 5 5762 (2014)
  4. ATM and ATR activities maintain replication fork integrity during SV40 chromatin replication. Sowd GA, Li NY, Fanning E. PLoS Pathog 9 e1003283 (2013)
  5. The human CTF4-orthologue AND-1 interacts with DNA polymerase α/primase via its unique C-terminal HMG box. Kilkenny ML, Simon AC, Mainwaring J, Wirthensohn D, Holzer S, Pellegrini L. Open Biol 7 170217 (2017)
  6. Crystal Structure of the Human Pol α B Subunit in Complex with the C-terminal Domain of the Catalytic Subunit. Suwa Y, Gu J, Baranovskiy AG, Babayeva ND, Pavlov YI, Tahirov TH. J Biol Chem 290 14328-14337 (2015)
  7. The C-terminal domain of the DNA polymerase catalytic subunit regulates the primase and polymerase activities of the human DNA polymerase α-primase complex. Zhang Y, Baranovskiy AG, Tahirov TH, Pavlov YI. J Biol Chem 289 22021-22034 (2014)
  8. Mini-chromosome maintenance complexes form a filament to remodel DNA structure and topology. Slaymaker IM, Fu Y, Toso DB, Ranatunga N, Brewster A, Forsburg SL, Zhou ZH, Chen XS. Nucleic Acids Res 41 3446-3456 (2013)
  9. Crystal structure of the human Polϵ B-subunit in complex with the C-terminal domain of the catalytic subunit. Baranovskiy AG, Gu J, Gu J, Babayeva ND, Kurinov I, Pavlov YI, Tahirov TH. J Biol Chem 292 15717-15730 (2017)
  10. The structure of SV40 large T hexameric helicase in complex with AT-rich origin DNA. Gai D, Wang D, Li SX, Chen XS. Elife 5 e18129 (2016)
  11. Contribution of DNA Replication to the FAM111A-Mediated Simian Virus 40 Host Range Phenotype. Tarnita RM, Wilkie AR, DeCaprio JA. J Virol 93 e01330-18 (2019)
  12. The conserved core enzymatic activities and the distinct dynamics of polyomavirus large T antigens. An P, Brodsky JL, Pipas JM. Arch Biochem Biophys 573 23-31 (2015)
  13. Novel interaction of the bacterial-Like DnaG primase with the MCM helicase in archaea. Bauer RJ, Graham BW, Trakselis MA. J Mol Biol 425 1259-1273 (2013)
  14. Amidst multiple binding orientations on fork DNA, Saccharolobus MCM helicase proceeds N-first for unwinding. Perera HM, Trakselis MA. Elife 8 e46096 (2019)
  15. SV40 T-antigen uses a DNA shearing mechanism to initiate origin unwinding. Langston LD, Yuan Z, Georgescu R, Li H, O'Donnell ME. Proc Natl Acad Sci U S A 119 e2216240119 (2022)
  16. SV40 T antigen helicase domain regions responsible for oligomerisation regulate Okazaki fragment synthesis initiation. Onwubiko NO, Scheffel F, Tessmer I, Nasheuer HP. FEBS Open Bio 12 649-663 (2022)
  17. Zn2+ blocks annealing of complementary single-stranded DNA in a sequence-selective manner. Lu S. Sci Rep 4 5464 (2014)
  18. Family D DNA polymerase interacts with GINS to promote CMG-helicase in the archaeal replisome. Oki K, Nagata M, Yamagami T, Numata T, Ishino S, Oyama T, Ishino Y. Nucleic Acids Res 50 3601-3615 (2022)
  19. Flexibility and Distributive Synthesis Regulate RNA Priming and Handoff in Human DNA Polymerase α-Primase. Cordoba JJ, Mullins EA, Salay LE, Eichman BF, Chazin WJ. J Mol Biol 435 168330 (2023)
  20. Modeling of the SV40 DNA Replication Machine. Simmons DT. Genes (Basel) 3 742-758 (2012)


Quick links