Et profilbilde

Professor
Svein Bjelland { "honorific-suffix": "Professor", "fn": "Svein Bjelland", "tel": "Telefon: 5183 1884", "email": "svein.bjelland@uis.no" }

Avdeling/enhet Det teknisk- naturvitenskapelige fakultet
Institutt/senter Institutt for matematikk og naturvitenskap
Rom KE E-528
Tlf priv/mob 47286404

Forskningsområder

Molecular Cancer Research Group, CORE

 

DNA damage and repair

Mutagenesis

 

Utvalgte publikasjoner

Selected scientific papers in the field of DNA damage, repair and mutagenesis

(*, corresponding author)

25. Moen MN, Knævelsrud I, Haugland GT, Grøsvik K, Birkeland N-K, Klungland A &

Bjelland S* (2011) Uracil-DNA glycosylase of Thermoplasma acidophilum directs

long-patch base excision repair, which is promoted by deoxynucleoside triphosphates and ATP/ADP, into short-patch repair. J. Bacteriol. 193, 4495-4508.

This paper describes long-patch base excision repair for the first time in Archaea.

24. Knævelsrud I, Moen MN, Grøsvik K, Haugland GT, Birkeland N-K, Klungland A,

Leiros I & Bjelland S* (2010) The hyperthermophilic euryarchaeon Archaeoglobus

fulgidus repairs uracil by single nucleotide replacement. J. Bacteriol. 192, 5755-5766.

23. Knævelsrud I, Slupphaug G, Leiros I, Matsuda A, Ruoff P & Bjelland S* (2009)

Opposite-base dependent excision of 5-formyluracil from DNA by hSMUG1. Int. J.

Radiat. Biol. 85, 413-420.

22. Ringvoll J, Moen MN, Nordstrand LM, Meira LB, Pang B, Bekkelund A, Dedon PC,

Bjelland S, Samson LD, Falnes PØ & Klungland A (2008) AlkB homolog 2 (ABH2)

mediated repair of ethenoadenine lesions in mammalian DNA. Cancer Res. 68, 4142-

4149.

21. Leiros I, Nabong MP, Grøsvik K, Ringvoll J, Haugland GT, Uldal L, Reite K,

Olsbu IK, Knævelsrud I, Moe E, Andersen OA, Birkeland N-K, Ruoff P, Klungland A

& Bjelland S* (2007) Structural basis for enzymatic excision of N1-methyladenine

and N3-methylcytosine from DNA. EMBO J. 26, 2206-2217.

This paper describes base excision repair of N1-methyladenine and N3-methylcytosine

for the first time.

20. Klungland A & Bjelland S (2007) Oxidative damage to purines in DNA: Role of

mammalian Ogg1. DNA Repair 6, 481-488 (Review).

19. Bjelland S* & Seeberg E (2003) Mutagenicity, toxicity and repair of DNA base

damage induced by oxidation. Mutat. Res. 531, 37-80 (Review).

This is the most comprehensive review paper on this topic, where an updated version

is presently being written.

18. Birkeland N-K, Ånensen H, Knævelsrud I, Kristoffersen W, Bjørås M, Robb FT,

Klungland A & Bjelland S* (2002) Methylpurine DNA glycosylase of the

hyperthermophilic archaeon Archaeoglobus fulgidus. Biochemistry 41, 12697-12705.

This is the first description of a hyperthermophilic methylpurine DNA glycosylase.

17. Knævelsrud I, Ruoff P, Ånensen H, Klungland A, Bjelland S* & Birkeland N-K

(2001) Excision of uracil from DNA by the hyperthermophilic Afung protein is

dependent on the opposite base and stimulated by heat-induced transition to a more

open structure. Mutat. Res. 487, 173-190.

16. Bjelland S*, Ånensen H, Knævelsrud I & Seeberg E (2001) Cellular effects of 5-

formyluracil in DNA. Mutat. Res. 486, 147-154 (Review).

15. Ånensen H, Provan F, Lian AT, Reinertsen S-HHS, Ueno Y, Matsuda A, Seeberg E &

Bjelland S* (2001) Mutations induced by 5-formyl-2´-deoxyuridine in Escherichia

coli include base substitutions that can arise from mispairs of 5-formyluracil with

guanine, cytosine and thymine. Mutat. Res. 476, 99-107.

14. Klungland A, Paulsen R, Rolseth V, Yamada Y, Ueno Y, Wiik P, Matsuda A, Seeberg

E & Bjelland S* (2001) 5-Formyluracil and its nucleoside derivatives confer toxicity

and mutagenicity to mammalian cells by interfering with normal RNA and DNA

metabolism. Toxicol. Lett. 119, 71-78.

12. Bjelland S* & Seeberg E (1996) Different efficiencies of the Tag and AlkA DNA

glycosylases from Escherichia coli in the removal of 3-methyladenine from singlestranded

DNA. FEBS Lett. 397, 127-129.

11. Bjelland S*, Eide L, Time RW, Stote R, Eftedal I, Volden G & Seeberg E (1995)

Oxidation of thymine to 5-formyluracil in DNA: Mechanisms of formation, structural

implications, and base excision by human cell free extracts. Biochemistry 34, 14758-

14764.

10. Bjelland S*, Birkeland N-K, Benneche T, Volden G & Seeberg E (1994) DNA

glycosylase activities for thymine residues oxidized in the methyl group are functions

of the AlkA enzyme in Escherichia coli. J. Biol. Chem. 269, 30489-30495.

This paper describes repair of the 5-formyluracil lesion for the first time.

9. Bjelland S*, Bjørås M & Seeberg E (1993) Excision of 3-methylguanine from

alkylated DNA by 3-methyladenine DNA glycosylase I of Escherichia coli.

Nucleic Acids Res. 21, 2045-2049.

8. Berdal KG, Bjørås M, Bjelland S & Seeberg E (1990) Cloning and expression in

Escherichia coli of a gene for an alkylbase DNA glycosylase from Saccharomyces

cerevisiae; a homologue to the bacterial alkA gene. EMBO J. 9, 4563-4568.

4. Bjelland S* & Seeberg E (1987) Purification and characterization of 3-methyladenine

DNA glycosylase I from Escherichia coli. Nucleic Acids Res. 15, 2787-2801.

Pågående forskning

Novel mechanisms in uracil-DNA base excision repair

All cells are essentially a complex aqueous solution of bio- and inorganic molecules and supra-molecular structures, confined by the plasma membrane. Thus, hydrolytic reactions are a demanding threat to many of its components including DNA. Next to base loss, deamination of cytosine to uracil is considered the primary DNA damaging event. Due to its ability to induce mutations following replication uracil must be faithfully repaired prior to replication by base excision repair (BER) initiated by uracil-DNA glycosylase (UDG), which was the first DNA glycosylase activity to be discovered about in the midst 1970ies. Since then, UDG has been grouped into several families distinguished by primary structure. All members of this UDG super-family have been described as mono-functional only exhibiting activity for removal of the damaged base from DNA. In contrast, bi-functional DNA glycosylases contains an accessory lyase function for incision of the resulting apurinic/apyrimidinic (AP) or abasic site. We have made the intriguing discovery that UDGs are able to incise uracil-containing DNA at the lesion site. Thus UDG can execute not only the first uracil excision step in BER, but also a second incision step, leaving behind a 3´-?,?-unsaturated aldehyde and a 5´-phosphate. The aim of the present project is to fully characterise these novel endonuclease activity of hUNG2 and hSMUG1 to possibly establish its function in uracil repair in vivo including cancer alleviation.

 

Mutation promotion by DNA excision repair indicates cancer-initiating ability

More than a decade ago, defects in mismatch repair genes were associated with hereditary nonpolyposis colon cancer, a relatively common type of malignant disease, thus defining certain repair genes as tumour suppressor genes. The first known cancer predisposition disorder associated with defects in the base excision repair (BER) pathway?the major repair mode for spontaneously generated lesions including oxidised bases in DNA?was eventually described. It was demonstrated that certain germ line mutations in the hMYH gene cause colorectal adenomas and cancer if both alleles are inactivated. This established a direct link between the mutagenicity/mispairing (with adenine) of a specific oxidative damage, i.e., 8-oxoguanine, and carcinogenesis. 5-formyluracil (fU) is another oxidative base damage present in DNA at similar concentrations as 8-oxoguanine. During studies of mutation induction in wild-type and repair-deficient bacteria by fU we made an interesting discovery. In addition to the anticipated role of the AlkA DNA glycosylase to alleviate mutation induction by initiating the BER pathway of this lesion, we found that such repair also actively contributes to mutagenesis. Importantly, preliminary evidence indicates that the same may be true for hSMUG1-initiated repair of fU in the DNA of human cells. Our discovery thus provides evidence to indicate that DNA repair genes, under certain circumstances, may function as oncogenes rather than tumour suppressor genes.

Arbeidserfaring

Professional experience

University of Stavanger, Faculty of Science and Technology, Department of Mathematics and

Natural Sciences, Stavanger, Norway, 2001: Professor in Biology (Associate Professor

from 1993); lecturer in microbiology/molecular biology, toxicology, gene technology,

DNA damage and repair/regulation and its relation to cancer; head of Chemical

Section 2000-2001

University of California, San Diego, University of California Cancer Center (Prof. Stephen

Howell), California, USA (2000): Visiting Scientist

University of California, Berkeley, Department of Molecular and Cell Biology (Prof. Stuart

Linn), California, U.S.A. (1999): Visiting Scientist

Stanford University School of Medicine, Department of Pathology, Laboratory of

Experimental Oncology (Prof. Errol C. Friedberg), California, U.S.A. (1989-1990):

Post.doc./Fellowship

Norwegian Defence Research Establishment (Prof. Erling Seeberg), Kjeller, Norway (1985-

1993): Research Associate/Fellowship

Institute of Clinical Medicine and Institute of Fisheries, University of Tromsø (Prof. Gunnar

Volden), Tromsø, Norway (1983-1985): Research Associate/ Fellowship

Norwegian Defence Microbiological Laboratory (Prof. Bjørn P. Berdal), Oslo, Norway

(1982): Research/Military Service

Vitenskapelige publikasjoner (fra CRISTin)

  • Moen, Marivi; Knævelsrud, Ingeborg; Haugland, Gyri Teien; Grøsvik, Kristin; Birkeland, Nils-Kåre; Klungland, Arne; Bjelland, Svein (2011). Uracil-DNA Glycosylase of Thermoplasma acidophilum Directs Long-Patch Base Excision Repair, Which Is Promoted by Deoxynucleoside Triphosphates and ATP/ADP, into Short-Patch Repair. Journal of Bacteriology. ISSN 0021-9193. Volum 193. Hefte 17. s. 4495-4508. DOI: 10.1128/JB.00233-11.
  • Knævelsrud, Ingeborg; Moen, Marivi; Grøsvik, Kristin; Haugland, Gyri Teien; Birkeland, Nils-Kåre; Klungland, Arne; Leiros, Ingar; Bjelland, Svein (2010). The Hyperthermophilic Euryarchaeon Archaeoglobus fulgidus Repairs Uracil by Single-Nucleotide Replacement. Journal of Bacteriology. ISSN 0021-9193. Volum 192. Hefte 21. s. 5755-5766. DOI: 10.1128/JB.00135-10.
  • Knævelsrud, I.; Slupphaug, Geir; Leiros, Ingar; Matsuda, A.; Ruoff, Peter; Bjelland, Svein (2009). Opposite-base dependent excision of 5-formyluracil from DNA by hSMUG1. International Journal of Radiation Biology. ISSN 0955-3002. Volum 85. Hefte 5. s. 413-420.
  • Ringvoll, Jeanette; Moen, Marivi N.; Nordstrand, Line M.; Meira, Lisiane B.; Pang, Bo; Bekkelund, Anders; Dedon, Peter C.; Bjelland, Svein; Samson, Leona D.; Falnes, Pål Ø.; Klungland, Arne (2008). AlkB homologue 2-mediated repair of ethenoadenine lesions in mammalian DNA. Cancer Research. ISSN 0008-5472. Volum 68. Hefte 11. s. 4142-4149.
  • Klungland, Arne; Bjelland, Svein (2007). Oxidative damage to purines in DNA: Role of mammalian Ogg1. DNA Repair. ISSN 1568-7864. Volum 6.
  • Leiros, Ingar; Nabong, Marivi P.; Grøsvik, Kristin; Ringvoll, Jeanette; Haugland, GT; Uldal, Lene; Reite, Karen; Olsbu, Inger K.; Knævelsrud, I.; Moe, Elin; Andersen, Ole A.; Birkeland, Nils-Kåre; Ruoff, Peter; Klungland, Arne; Bjelland, Svein (2007). Structural basis for enzymatic excision of N-1-methyladenine and N-3-methylcytosine from DNA. EMBO Journal. ISSN 0261-4189. Volum 26.
  • Bjelland, Svein; Seeberg, E. (2003). Mutagenicity, toxicity and repair of DNA base damage induced by oxidation. Mutation research. Reviews in mutation research. ISSN 1383-5742. Volum 531. s. 37-80.
  • Birkeland, Nils-Kåre; Ånensen, Hilde; Knævelsrud, Ingeborg; Kristoffersen, Wenche; Bjørås, M.; Robb, F.T.; Klungland, Arne; Bjelland, Svein (2002). Methylpurine DNA glycosylase of the hyperthermophilic archaeon Archaeoglobus fulgidus. Biochemistry. ISSN 1520-4995. Volum 41. s. 12697-12705.
  • Bjelland, S.; Knævelsrud, I.; Seeberg, E. (2001). Cellular effects of 5-formyluracil in DNA (Review). Mutation research. Reviews in mutation research. ISSN 1383-5742. Volum 486. s. 147-154.
  • Bjelland, Svein; Klungland, Arne; Paulsen, R.; Rolseth, V.; Yamada, Y.; Ueno, Y.; Wiik, P.; Matsuda, A.; Seeberg, E. (2001). 5-Formyluracil and its nucleoside derivatives confer toxicity and mutagenicity to mammalian cells by interfering with normal RNA and DNA metabolism. Toxicology Letters. ISSN 0378-4274. Volum 119. s. 71-78.
  • Bjelland, Svein; Ånensen, Hilde; Knævelsrud, Ingeborg; Seeberg, E. (2001). Cellular effects of 5-formyluracil in DNA. Mutation research. Reviews in mutation research. ISSN 1383-5742. Volum 486. s. 147-154.
  • Knævelsrud, I.; Ruoff, Peter; ukjent-for-m012243, ukjent-for-m012243; Klungland, A.; Birkeland, N.-K. (2001). Excision of uracil from DNA by the hyperthermophilic Afung protein is dependent on the opposite base and stimulated by heat-induced transition to a more open structure. Excision of uracil from DNA by the hyperthermophilic Afung protein is dependent on the opposite base and stimulated by heat-induced transition to a more open structure. Volum 487. s. 173-190.
  • ukjent-for-m012243, ukjent-for-m012243; Provan, Fiona; Lian, A.T.; Reinertsen, S.-H.H.S; Ueno, Y.; Matsuda, A.; Seeberg, E. (2001). Mutations induced by 5-formyl-2´-deoxyuridine in Escherichia coli include base substitutions that can arise from mispairs of 5-formyluracil with guanine, cytosine and thymine. Mutation research. Reviews in mutation research. ISSN 1383-5742. Volum 476. s. 99-107.
  • Bjelland, Svein; Seeberg, E. (1996). Different efficiencies of the Tag and AlkA DNA glycosylases from Escherichia coli in the removal of 3-methyladenine from single-stranded DNA. FEBS Letters. ISSN 0014-5793. Volum 397. s. 127-129.
  • Bjelland, Svein; Birkeland, N.-K.; Benneche, T.; Volden, G.; Seeberg, E. (1994). DNA glycosylase activities for thymine residues oxidized in the methyl group are functions of the AlkA enzyme in Escherichia coli. Journal of Biological Chemistry. ISSN 0021-9258. Volum 269. s. 30489-30495.
  • Bjørås, M.; Berdal, K.G.; Bjelland, Svein; Seeberg, E. (1990). Cloning and expression in Escherichia coli of a gene for an alkylbase DNA glycosylase from Saccharomyces cerevisiae; a homologue to the bacterial alkA gene. EMBO Journal. ISSN 0261-4189. Volum 9. s. 4563-4568.
  • Bjelland, Svein (1997). Base excision repair of DNA damage induced by alkylating and oxidative agents. Universitetet i Oslo.
  • Alexeeva, Marina; Moen, Marivi Nabong; Xu, Xiang Ming; Rasmussen, Anette; Kirpekar, Finn; Klungland, Arne; Bjelland, Svein (2017). hSMUG1 is a bi-functional DNA glycosylase. Norwegian Biochemical Society; 2017-01-19 - 2017-01-22.
  • Tesfahun, Almaz Nigatu; Klungland, Arne; Klimasauskas, Saulius; Bjelland, Svein (2017). Repair of double methylated bases in DNA. Norwegian Biochemical Society; 2017-01-19 - 2017-01-22.
  • Alexeeva, Maria; Tesfahun, Almaz Nigatu; Bjelland, Svein (2016). DNA uracil excision includes strand incision by hUNG and hSMUG1. Vilnius University;
  • Alexeeva, Marina; Moen, Marivi Nabong; Xu, Xiang Ming; Rasmussen, Anette; Kirpekar, Finn; Klungland, Arne; Bjelland, Svein (2016). hSMUG1-catalysed uracil-DNA strand incision. 2016-08-25 - 2016-08-28.
  • Alexeeva, Marina; Moen, Marivi Nabong; Xu, Xiang Ming; Rasmussen, Anette; Kirpekar, Finn; Klungland, Arne; Bjelland, Svein (2016). hSMUG1-catalysed uracil-DNA strand incision. FEBS; 2016-10-03 - 2016-10-08.
  • Tesfahun, Almaz Nigatu; Alexeeva, Marina; Bjelland, Svein (2016). Repair of double methylated bases in DNA. Vilnius University;
  • Tesfahun, Almaz Nigatu; Klungland, Arne; Klimasauskas, Saulius; Bjelland, Svein (2016). Repair of double methylated bases in DNA. 7th Annual BioStruct Conference; 2016-08-25 - 2016-08-28.
  • Bjelland, Svein (2015). "The king of base excision repair" fikk omsider Nobelprisen i år. Norsk Kjemisk Selskap; 2015-12-11.
  • Knævelsrud, Ingeborg; Kazazic, Sabina; Birkeland, Nils-Kåre; Bjelland, Svein (2014). The pH optimum of native uracil-DNA glycosylase of Archaeoglobus fulgidus compared to recombinant enzyme indicates adaption to cytosolic pH.
  • Muruzábal-Lecumberri, Izaskun; Grøsvik, Kristin; Matsuda, Akira; Bjelland, Svein (2014). Alleviation and promotion of damage-specific mutation induction in Escherichia coli are dependent on the uvrA gene. 2014-11-12 - 2014-11-16.
  • Bjelland, Svein (2010). Base excision repair in euryarchaeons. 2010-05-22.
  • Bjelland, Svein (2010). Tungvint kreftbehandling.
  • Leiros, Ingar; Nabong, Marivi P.; Haugland, GT; Ringvoll, Jeanette; Grøsvik, K; Grøsvik, K; Moe, Elin; Knævelsrud, I.; Knævelsrud, I.; Reite, Karen; Andersen, Ole A.; Birkeland, Nils-Kåre; Klungland, Arne; Bjelland, Svein; Bjelland, Svein (2006). Excision of 1-methyladenine and 3-methylcytosine from DNA by AfAlkA of Archaeoglobus fulgidus. 2006-05-30 - 2006-06-05.
  • Knævelsrud, I.; Klungland, A.; Birkeland, N.-K.; Bjelland, Svein (2005). Excision of dUMP from DNA by the hyperthermophilic archaeon Archaeoglobus fulgidus. 2005-11-30 - 2005-12-02.
  • Knævelsrud, I.; Haugland, GT; Birkeland, N.-K.; Bjelland, Svein (2004). Excision of dUMP from DNA by the hyperthermophilic archaeon Archaeoglobus fulgidus. 2004-11-14 - 2004-11-20.
  • Knævelsrud, Ingeborg; Birkeland, Nils-Kåre; Bjelland, Svein (2003). Afung represents the principal uracil DNA glycosylase enzyme present in the hyperthermophilic archaeon Archaeoglobus fu. 2003-09-15 - 2003-09-19.
  • Birkeland, Nils-Kåre; Ånensen, Hilde; Kristoffersen, Wenche; Knævelsrud, Ingeborg; Bjørås, M.; Klungland, Arne; Robb, F.T.; Bjelland, Svein (2002). Cold-active methylpurine DNA glycosylase of the hyperthermophilic archaeon Archaeoglobus fulgidus. 2002-09-22 - 2002-09-26.
  • Knævelsrud, Ingeborg; Bjelland, Svein; Birkeland, Nils-Kåre (2001). Uracil-DNA glycosylase from the hyperthermophilic archaeon Archaeoglobus fulgidus.
  • Bjelland, Svein; Klungland, A.; Provan, Fiona; Lian, A. T.; Ånensen, H.; Selmer, S.-H.; Wiik, P.; Ueno, Y.; Matsuda, A.; Seeberg, E. (1998). Addition of 5-formyldeoxyuridine to the growth medium of bacteria and mammalian cells causes mutations.
  • Bjelland, Svein; Klungland, A.; Ueno, Y.; Matsuda, A.; Seeberg, E. (1998). 5-Formyldeoxyuridine-induced mutagenesis in bacteria and mammalian cells.
  • Bjelland, Svein; Klungland, A.; Ånensen, H.; Provan, Fiona; Selmer, S.-H.; Lian, A.T.; Wiik, P.; Ueno, Y.; Matsuda, A.; Seeberg, E. (1998). 5-formyldeoxyuridine-induced mutagenesis in bacteria and mammalian cells.
  • Bjelland, Svein (1996). Mutagenicity of an oxidized thymine base and its nucleoside-5 -formyluracil and 5-formyldeoxyuridine- to mammalian cells. 1996-01-21.