Erik Johansson - Professor

Deputy Head of Department

DNA polymerase
 

The diploid human genome has been estimated to contain 6 billion nucleotides. It is an enormous task for the proliferating cell to replicate the entire genome, due to the size and accuracy by which it must be accomplished. It must also be a very efficient process because the cell has a very limited time to finish the task. We are studying on the molecular level how DNA replication is accomplished in eukaryotic cells. There still remain many large questions that have not been completely resolved. It is not entirely known how DNA replication is initiated, or how a replication fork functions. We are focused on the proteins that participate at the eukaryotic replication fork. Our main focus lies on DNA polymerase epsilon that plays a role at the replication fork.

Our main goals are, (i) to understand how DNA polymerase epsilon interacts with other replication fork proteins, (ii) to understand how DNA polymerase epsilon participates at the replication fork and if DNA polymerase epsilon fulfills some other important function during the replication of the chromosomes, (iii) to understand how DNA polymerase epsilon contributes to the fidelity of the replication of the genome, (iv) to understand how DNA polymerase epsilon is involved in DNA repair processes and cell-cycle regulation. Our model system is S. cerevisiae and this allows us to complement our biochemical characterizations with yeast genetics in in vivo experiments.

Group:
Göran Bylund
Pia Osterman
Vimal Parkash
Josy ter Beek
 

Publications

1. Ganai, R.A., Zhang, X.P., Heyer, W.D. and Johansson, E. (2016) Strand displacement synthesis by yeast DNA polymerase ε. Nucleic Acids Res. 44:8229-40

2. Ganai, R.A. and Johansson, E. (2016) DNA Replication-A Matter of Fidelity. Mol Cell. 62:745-55

3. Rentoft, M., Lindell, K., Tran, P., Chabes, A.L., Buckland, R.J., Watt, D.L., Marjavaara, L., Nilsson, A.K., Melin, B., Trygg, J., Johansson, E. and Chabes, A. (2016) Heterozygous colon cancer-associated mutations of SAMHD1 have functional significance. Proc Natl Acad Sci U S A. 113:4723-8

4. Ganai, R.A., Bylund, G.O., and Johansson, E. (2015) Switching between polymerase and exonuclease rates in DNA polymerase epsilon. Nucleic Acids Res 43:932-42

5. Ganai, R.A., Osterman, P., and Johansson, E. (2015) Yeast DNA polymerase epsilon catalytic core and holoenzyme have comparable catalytic rates. J. Biol. Chem. 290:3825-35

6. Yousefzadeh MJ, Wyatt DW, Takata K, Mu Y, Hensley SC, Tomida J, Bylund GO, Doublié S, Johansson E, Ramsden DA, McBride KM,  and Wood RD. (2014) 
Mechanism of Suppression of Chromosomal Instability by DNA Polymerase POLQ. PLoS Genet. 10:e1004654

7. Hogg, M., Osterman, P., Bylund, G.O., Ganai, R.A., Lundström, E.-B., Sauer- Eriksson, A.E. and Johansson, E. (2014) Structural basis for processive DNA synthesis by yeast DNA polymerase epsilon. Nature Structural & Molecular Biology 21:49-55

8. Johansson, E. and Dixon, N. (2013) Replicative DNA polymerases. Cold Spring Harb Perspect Biol. 2013 Jun 1;5(6). doi:pii: a012799. 10.1101/cshperspect.a012799. PMID: 237322474

9. Isoz, I, Persson, U., Volkov, K. and Johansson, E. (2012) The C-terminus of Dpb2 is required for interaction with Pol2 and for cell viability. Nucleic Acids Res. 40:11545-53

10. Sparks, J.L., Chon, H., Cerritelli, S.M., Kunkel, T.A., Johansson, E., Crouch, R.J., and Burgers, P.M. (2012) RNase H2-Initiated Ribonucleotide Excision Repair. Mol. Cell. 47:980-986.

11. Hogg, M., and Johansson, E. (2012) DNA polymerase ε; The Eukaryotic Replisome: a Guide to Protein Structure and Function, edited by Stuart MacNeill Springer, Netherlands, DOI: 10.1007/978-94-007-4572-8_13, Subcellular biochemistry 62:237-257

12. Williams, J.S., Clausen, A.R. Nick McElhinny, S.A.,Watts, B.E, Johansson, E., and Kunkel, T.A. (2012) Proofreading of ribonucleotides inserted into DNA by yeast DNA polymerase ε. DNA Repair 11:649-56

13. Hogg, M, Sauer-Eriksson, A.E., and Johansson, E. (2012) Promiscuous DNA synthesis by human DNA polymerase θ. Nucleic Acids Res. 40: 2611-2622

14. Watt DL, Johansson E, Burgers PM, Kunkel TA. (2011) Replication of ribonucleotide-containing DNA templates by yeast replicative polymerases. DNA Repair (Amst) 15;10(8):897-902. PMID: 21703943

15. Johansson E, Speck C, Chabes A. (2011) A top-down view on DNA replication and recombination from 9,000 feet above sea level. Genome Biol 12(4):304 PMID: 21554750 [PubMed - in process]

16. Aksenova, A., Volkov, K., Macheluch, J., Pursell, Z.F., Rogozin, I.B., Kunkel, T.A., Pavlov, Y.I. and Johansson, E. (2010) Mismatch repair-independent increase in spontaneous mutagenesis in yeast lacking non-essential subunits of DNA polymerase epsilon. PLoS Genetics doi:10.1371/journal.pgen.1001209

17. Nick McElhinny, S.A., Kumar, D., Clark, A.B., Watt, D.L., Watts, B.E., Lundström, E.B., Johansson, E., Chabes, A., Kunkel, TA. (2010) The consequences of rNMP incorporation into DNA in vivo by yeast DNA polymerase epsilon. Nature Chemical Biology 10:774-81

18. Nick McElhinny, S.A., Watts, B., Kumar, D., Watt, D., Lundström, E.B., Burgers, P.M.J., Johansson, E., Chabes, A., & Kunkel, T.A. (2010 Mar 16; Epub 2010 Mar 1). Abundant ribonucleotide incorporation into DNA by yeast replicative polymerases. Proc Natl Acad Sci U S A. 107(11), 4949-4954.

19. Johansson, E. and MacNeil, SA. (2010) The eukaryotic replicative DNA polymerases take shape. Trends in Biochemical Sciences (TiBS) 35:339-47.

20. Sabouri, N. and Johansson E. (2009) Translesion synthesis of abasic sites by yeast DNA polymerase epsilon. J. Biol. Chem. 284:31555-63.

21. Sabouri, N., Viberg, J., Kumar, D., Johansson, E., and Chabes, A. (2008) Evidence for lesion bypass by yeast replicative DNA plymerases during DNA damage. Nucleic Acids Res. 36:5660-7.

22. Wardle, J., Burgers, P.M.J., Cann, I.K.O., Darley, K., Heslop, P., Johansson, E., Lin, L.-J., McGlynn, P., Sanvoisin, J., Stith, C.M., and Connolly, B.A. (2008) Uracil recognition by replicative DNA polymerase is limited to the archaea, not occurring with bacteria and eukarya. Nucleic Acids Res. 36:705-11.

23. Chilkova, O., Stenlund, P., Isoz, I., Stitch, C., Grabowski, P., Lundström, E.-B., Burgers, P.M., and Johansson, E. (2007) The eukaryotic leading and lagging strand DNA polymerases are loaded onto primer-ends via separate mechanisms but have comparable processivity in the presence of PCNA. Nucleic Acids Res. 35:6588-6597.

24. Pursell, Z.F., Isoz, I., Lundström, E.-B., Johansson, E., and Kunkel, T.A. (2007) Yeast DNA polymerase epsilon participates in leading-strand DNA replication. Science 317:127-130.

25. Pursell, Z.F., Isoz, I., Lundström, E.-B., Johasson, E., and Kunkel, T.A. (2007) Regulation of B Family DNA Polymerase Fidelity by a Conserved Active Site Residue: Characterization of M644W, M644L and M644F Mutants of Yeast DNA Polymerase epsilon. Nucleic Acids Res. 35:3076-3086.

26. Asturias, F.J., Cheung, I.K., Sabouri, N., Chilkova, O., Wepplo, D., and Johansson, E. (2006) Structure of Saccharomyces cerevisiae DNA polymerase epsilon by cryo-electron microscopy. Nature Structural and Molecular Biology 13:35-43.

27. Fortune, J.M., Pavlov, Y.I., Welch, C.M., Johansson, E. and Burgers, P.M.J., and Kunkel, T.A. (2005) Saccharomyces cerevisiae DNA polymerase d : High fidelity for base substitutions but lower fiderlity for single- and multi-base deletions. J. Biol. Chem. 280:29980-29987.

28. Garg, P., Stith, C.M., Sabouri, N., Johansson, E., and Burgers, P.M. (2004) Idling by DNA polymerase d maintains a ligatable nick during lagging-strand DNA replication. Genes & Dev 18:2764-2773.

29. MacCulloch, S.D., Kokoska, R.J., Chilkova, O., Welch, C.M., Johansson, E., Burgers, P.M., and Kunkel, T.A. (2004) Enzymatic switching for efficient and accurate translesion DNA replication. Nucleic Acids Res. 32:4665-4675.

30. Johansson, E., Garg, P., and Burgers, P.M.J. (2004) The Pol32 subunit of DNA polymerase delta contains separable domains for processive replication and profliferating cell nuclear antigen (PCNA) binding. J. Biol. Chem. 279:1907-1915.

31. Shcherbakova, P.V., Pavlov, Y.I., Chilkova, O., Rogozin, I.B., Johansson, E., and Kunkel, T.A. (2003) Unique error signature of the four-subunit yeast DNA polymerase epsilon. J. Biol. Chem. 278:43770-43780.

32. Chilkova, O., Jonsson, B.-H., and Johansson, E. (2003) The quaternary structure of DNA polymerase epsilon from S. cerevisiae. J. Biol. Chem. 278:14082-14086.2


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Medical Biochemistry and Biophysics
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