Conformational flexibility of fork-remodeling helicase Rad5 shown by full-ensemble hybrid methods


Autoři: Melissa S. Gildenberg aff001;  M. Todd Washington aff001
Působiště autorů: Department of Biochemistry, University of Iowa College of Medicine, Iowa City, Iowa, United States of America aff001
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223875

Souhrn

Several pathways exist to bypass DNA damage during replication. One such pathway is template switching. The Rad5 protein plays two important roles in template switching: it is an E3 ubiquitin ligase that catalyzes PCNA poly-ubiquitylation and it is a helicase that converts replication forks to chicken foot structures. To understand the structure, conformational flexibility, and mechanism of Rad5, we used a full-ensemble hybrid method combining Langevin dynamics simulations and small-angle X-ray scattering. From these studies, we generated the first experimentally validated, high-resolution structural model of Rad5. We found that Rad5 is more compact and less extended than is suggested by its large amount of predicted intrinsic disorder. Thus, Rad5 likely has a novel intra-molecular interaction that limits the range of conformational space it can sample. We provide evidence for a novel interaction between the HIRAN and the helicase domains of Rad5, and we discuss the biological and mechanistic implications of this.

Klíčová slova:

Biochemical simulations – Biophysical simulations – Cross-linking – DNA damage – DNA replication – Helicases – Simulation and modeling – Small-angle scattering


Zdroje

1. Hoege C., Pfander B., Moldovan G. L., Pyrowolakis G., and Jentsch S. (2002) RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO. Nature 419, 135–141 doi: 10.1038/nature00991 12226657

2. Stelter P., and Ulrich H. D. (2003) Control of spontaneous and damage-induced mutagenesis by SUMO and ubiquitin conjugation. Nature 425, 188–191 doi: 10.1038/nature01965 12968183

3. Bergink S., and Jentsch S. (2009) Principles of ubiquitin and SUMO modifications in DNA repair. Nature 458, 461–467 doi: 10.1038/nature07963 19325626

4. Ulrich H. D., and Walden H. (2010) Ubiquitin signalling in DNA replication and repair. Nature reviews. Molecular cell biology 11, 479–489 doi: 10.1038/nrm2921 20551964

5. Dieckman L. M., Freudenthal B. D., and Washington M. T. (2012) PCNA structure and function: insights from structures of PCNA complexes and post-translationally modified PCNA. Sub-cellular biochemistry 62, 281–299 doi: 10.1007/978-94-007-4572-8_15 22918591

6. Boehm E. M., Gildenberg M. S., and Washington M. T. (2016) The Many Roles of PCNA in Eukaryotic DNA Replication. The Enzymes 39, 231–254 doi: 10.1016/bs.enz.2016.03.003 27241932

7. Prakash S., and Prakash L. (2002) Translesion DNA synthesis in eukaryotes: a one- or two-polymerase affair. Genes & development 16, 1872–1883

8. Prakash S., Johnson R. E., and Prakash L. (2005) Eukaryotic translesion synthesis DNA polymerases: specificity of structure and function. Annual review of biochemistry 74, 317–353 doi: 10.1146/annurev.biochem.74.082803.133250 15952890

9. Lehmann A. R. (2005) Replication of damaged DNA by translesion synthesis in human cells. FEBS letters 579, 873–876 doi: 10.1016/j.febslet.2004.11.029 15680966

10. Lehmann A. R., Niimi A., Ogi T., Brown S., Sabbioneda S., Wing, et al. (2007) Translesion synthesis: Y-family polymerases and the polymerase switch. DNA repair 6, 891–899 doi: 10.1016/j.dnarep.2007.02.003 17363342

11. Guo C., Kosarek-Stancel J. N., Tang T. S., and Friedberg E. C. (2009) Y-family DNA polymerases in mammalian cells. Cellular and molecular life sciences: CMLS 66, 2363–2381 doi: 10.1007/s00018-009-0024-4 19367366

12. Waters L. S., Minesinger B. K., Wiltrout M. E., D’Souza S., Woodruff R. V., and Walker G. C. (2009) Eukaryotic translesion polymerases and their roles and regulation in DNA damage tolerance. Microbiology and molecular biology reviews: MMBR 73, 134–154 doi: 10.1128/MMBR.00034-08 19258535

13. Washington M. T., Carlson K. D., Freudenthal B. D., and Pryor J. M. (2010) Variations on a theme: eukaryotic Y-family DNA polymerases. Biochimica et biophysica acta 1804, 1113–1123 doi: 10.1016/j.bbapap.2009.07.004 19616647

14. Sale J. E., Lehmann A. R., and Woodgate R. (2012) Y-family DNA polymerases and their role in tolerance of cellular DNA damage. Nature reviews. Molecular cell biology 13, 141–152 doi: 10.1038/nrm3289 22358330

15. Pryor J. M., Dieckman L. M., Boehm E. M., and Washington M. T. (2014) Eukaryotic Y-Family Polymerases: A Biochemical and Structural Perspective. Nucleic Acids Mol Bi 30, 85–108

16. Powers K. T., and Washington M. T. (2018) Eukaryotic translesion synthesis: Choosing the right tool for the job. DNA repair 71, 127–134 doi: 10.1016/j.dnarep.2018.08.016 30174299

17. Blastyak A., Pinter L., Unk I., Prakash L., Prakash S., and Haracska L. (2007) Yeast Rad5 protein required for postreplication repair has a DNA helicase activity specific for replication fork regression. Molecular cell 28, 167–175 doi: 10.1016/j.molcel.2007.07.030 17936713

18. Kile A. C., Chavez D. A., Bacal J., Eldirany S., Korzhnev D. M., Bezsonova I., et al. (2015) HLTF’s Ancient HIRAN Domain Binds 3' DNA Ends to Drive Replication Fork Reversal. Molecular cell 58, 1090–1100 doi: 10.1016/j.molcel.2015.05.013 26051180

19. Unk I., Hajdu I., Blastyak A., and Haracska L. (2010) Role of yeast Rad5 and its human orthologs, HLTF and SHPRH in DNA damage tolerance. DNA repair 9, 257–267 doi: 10.1016/j.dnarep.2009.12.013 20096653

20. Gangavarapu V., Haracska L., Unk I., Johnson R. E., Prakash S., and Prakash L. (2006) Mms2-Ubc13-dependent and -independent roles of Rad5 ubiquitin ligase in postreplication repair and translesion DNA synthesis in Saccharomyces cerevisiae. Molecular and cellular biology 26, 7783–7790 doi: 10.1128/MCB.01260-06 16908531

21. Ball L. G., Xu X., Blackwell S., Hanna M. D., Lambrecht A. D., and Xiao W. (2014) The Rad5 helicase activity is dispensable for error-free DNA post-replication repair. DNA repair 16, 74–83 doi: 10.1016/j.dnarep.2014.02.016 24674630

22. Ishida T., and Kinoshita K. (2007) PrDOS: prediction of disordered protein regions from amino acid sequence. Nucleic acids research 35, W460–464 doi: 10.1093/nar/gkm363 17567614

23. Ishida T., and Kinoshita K. (2008) Prediction of disordered regions in proteins based on the meta approach. Bioinformatics 24, 1344–1348 doi: 10.1093/bioinformatics/btn195 18426805

24. Powers K. T., Elcock A. H., and Washington M. T. (2018) The C-terminal region of translesion synthesis DNA polymerase eta is partially unstructured and has high conformational flexibility. Nucleic acids research 46, 2107–2120 doi: 10.1093/nar/gky031 29385534

25. Powers K. T., Lavering E. D., and Washington M. T. (2018) Conformational Flexibility of Ubiquitin-Modified and SUMO-Modified PCNA Shown by Full-Ensemble Hybrid Methods. Journal of molecular biology 430, 5294–5303 doi: 10.1016/j.jmb.2018.10.017 30381149

26. Powers K. T., Gildenberg M. S., and Washington M. T. (2019) Modeling Conformationally Flexible Proteins With X-ray Scattering and Molecular Simulations. Comput Struct Biotechnol J 17, 570–578 doi: 10.1016/j.csbj.2019.04.011 31073392

27. Nielsen S. S., Toft K. N., Snakenborg D., Jeppesen M. G., Jacobsen J. K., Vestergaard B., et al. (2009) BioXTAS RAW, a software program for high-throughput automated small-angle X-ray scattering data reduction and preliminary analysis. J Appl Crystallogr 42, 959–964

28. Konarev P. V., Volkov V. V., Sokolova A. V., Koch M. H. J., and Svergun D. I. (2003) PRIMUS: a Windows PC-based system for small-angle scattering data analysis. J Appl Crystallogr 36, 1277–1282

29. Petoukhov M. V., Konarev P. V., Kikhney A. G., and Svergun D. I. (2007) ATSAS 2.1—towards automated and web-supported small-angle scattering data analysis. J Appl Crystallogr 40, S223–S228

30. Svergun D. I. (1992) Determination of the Regularization Parameter in Indirect-Transform Methods Using Perceptual Criteria. J Appl Crystallogr 25, 495–503

31. McGinty R. K., Henrici R. C., and Tan S. (2014) Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome. Nature 514, 591–596 doi: 10.1038/nature13890 25355358

32. Thoma N. H., Czyzewski B. K., Alexeev A. A., Mazin A. V., Kowalczykowski S. C., and Pavletich N. P. (2005) Structure of the SWI2/SNF2 chromatin-remodeling domain of eukaryotic Rad54. Nature structural & molecular biology 12, 350–356

33. Willhoft O., Ghoneim M., Lin C. L., Chua E. Y. D., Wilkinson M., Chaban Y., et al. (2018) Structure and dynamics of the yeast SWR1-nucleosome complex. Science 362

34. Hauk G., McKnight J. N., Nodelman I. M., and Bowman G. D. (2010) The chromodomains of the Chd1 chromatin remodeler regulate DNA access to the ATPase motor. Molecular cell 39, 711–723 doi: 10.1016/j.molcel.2010.08.012 20832723

35. Farnung L., Vos S. M., Wigge C., and Cramer P. (2017) Nucleosome-Chd1 structure and implications for chromatin remodelling. Nature 550, 539–542 doi: 10.1038/nature24046 29019976

36. Eustermann S., Schall K., Kostrewa D., Lakomek K., Strauss M., Moldt M., et al. (2018) Structural basis for ATP-dependent chromatin remodelling by the INO80 complex. Nature 556, 386–390 doi: 10.1038/s41586-018-0029-y 29643509

37. Butryn A., Woike S., Shetty S. J., Auble D. T., and Hopfner K. P. (2018) Crystal structure of the full Swi2/Snf2 remodeler Mot1 in the resting state. Elife 7

38. Kelley L. A., Mezulis S., Yates C. M., Wass M. N., and Sternberg M. J. (2015) The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc 10, 845–858 doi: 10.1038/nprot.2015.053 25950237

39. Kozakov D., Hall D. R., Xia B., Porter K. A., Padhorny D., Yueh C., et al. (2017) The ClusPro web server for protein-protein docking. Nat Protoc 12, 255–278 doi: 10.1038/nprot.2016.169 28079879

40. Pierce B. G., Wiehe K., Hwang H., Kim B. H., Vreven T., and Weng Z. (2014) ZDOCK server: interactive docking prediction of protein-protein complexes and symmetric multimers. Bioinformatics 30, 1771–1773 doi: 10.1093/bioinformatics/btu097 24532726

41. Frembgen-Kesner T., and Elcock A. H. (2009) Striking Effects of Hydrodynamic Interactions on the Simulated Diffusion and Folding of Proteins. Journal of chemical theory and computation 5, 242–256 doi: 10.1021/ct800499p 26610102

42. Svergun D., Barberato C., and Koch M. H. J. (1995) CRYSOL—A program to evaluate x-ray solution scattering of biological macromolecules from atomic coordinates. J Appl Crystallogr 28, 768–773

43. Eng J. K., McCormack A. L., and Yates J. R. (1994) An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database. J Am Soc Mass Spectrom 5, 976–989 doi: 10.1016/1044-0305(94)80016-2 24226387

44. Perkins D. N., Pappin D. J., Creasy D. M., and Cottrell J. S. (1999) Probability-based protein identification by searching sequence databases using mass spectrometry data. Electrophoresis 20, 3551–3567 doi: 10.1002/(SICI)1522-2683(19991201)20:18<3551::AID-ELPS3551>3.0.CO;2-2 10612281

45. Bern M., Kil Y. J., and Becker C. (2012) Byonic: advanced peptide and protein identification software. Curr Protoc Bioinformatics Chapter 13, Unit13 20 doi: 10.1002/0471250953.bi1320s40 23255153

46. Biasini M., Bienert S., Waterhouse A., Arnold K., Studer G., Schmidt T., et al. (2014) SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic acids research 42, W252–258 doi: 10.1093/nar/gku340 24782522

47. Brosey C. A., Yan C., Tsutakawa S. E., Heller W. T., Rambo R. P., Tainer J. A., et al. (2013) A new structural framework for integrating replication protein A into DNA processing machinery. Nucleic acids research 41, 2313–2327 doi: 10.1093/nar/gks1332 23303776

48. Beyer D. C., Ghoneim M. K., and Spies M. (2013) Structure and Mechanisms of SF2 DNA Helicases. Adv Exp Med Biol 767, 47–73 doi: 10.1007/978-1-4614-5037-5_3 23161006

49. Xu X., Lin A., Zhou C., Blackwell S. R., Zhang Y., Wang Z., et al. (2016) Involvement of budding yeast Rad5 in translesion DNA synthesis through physical interaction with Rev1. Nucleic acids research

50. Moldovan G. L., Pfander B., and Jentsch S. (2007) PCNA, the maestro of the replication fork. Cell 129, 665–679 doi: 10.1016/j.cell.2007.05.003 17512402


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