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The Schizosaccharomyces pombe replication inhibitor Spd1 regulates ribonucleotide reductase activity and dNTPs by binding to the large Cdc22 subunit.
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
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2006 (Engelska)Ingår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 281, nr 3, s. 1778-1783Artikel i tidskrift (Refereegranskat) Published
Ort, förlag, år, upplaga, sidor
2006. Vol. 281, nr 3, s. 1778-1783
Nyckelord [en]
Cell Cycle Proteins/genetics/*metabolism/*physiology, Cloning; Molecular, DNA Replication, Deoxyribonucleotides/*metabolism, Escherichia coli/genetics, G1 Phase, Kinetics, Protein Subunits/metabolism, Recombinant Proteins/isolation & purification/metabolism, Ribonucleotide Reductases/antagonists & inhibitors/genetics/*metabolism, Schizosaccharomyces/cytology/enzymology/*genetics, Schizosaccharomyces pombe Proteins/genetics/*metabolism/*physiology
Identifikatorer
URN: urn:nbn:se:umu:diva-6344DOI: 10.1074/jbc.M511716200PubMedID: 16317005Scopus ID: 2-s2.0-33644972445OAI: oai:DiVA.org:umu-6344DiVA, id: diva2:146013
Tillgänglig från: 2007-12-09 Skapad: 2007-12-09 Senast uppdaterad: 2023-03-23Bibliografiskt granskad
Ingår i avhandling
1. Ribonucleotide reductase and DNA damage
Öppna denna publikation i ny flik eller fönster >>Ribonucleotide reductase and DNA damage
2006 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

A prerequisite for a multicellular organism to survive is the ability to correctly replicate and repair DNA while minimizing the number of heritable mutations. To achieve this, cells need a balanced supply of deoxyribonucleoside triphosphates (dNTPs), the precursors for DNA synthesis. The rate-limiting step in de novo biosynthesis of dNTPs is catalyzed by the enzyme ribonucleotide reductase (RNR).

The classic eukaryotic RNR enzyme consists of a large and a small subunit. Together, these subunits form a heterotetrameric RNR complex. The larger subunit harbours active sites whereas the smaller subunit contains a stable tyrosyl free radical. Both subunits are required for RNR activity.

Since failure to correctly regulate de novo dNTP biosynthesis can lead to misincorporation of nucleotides into DNA, genetic abnormalities and cell death, RNR activity is tightly regulated. The regulation of RNR activity involves cell cycle-specific expression and degradation of the RNR proteins, as well as binding of allosteric effectors to the large RNR subunit.

In this thesis, in vitro assays based on purified recombinant RNR proteins, in combination with in vivo assays, have been used successfully to study the regulation of RNR activity in response to DNA damage. I present new findings regarding the function of an alternative mammalian RNR small subunit, and on the role of a small RNR inhibitor protein of fission yeast, during normal growth and after DNA damage. I also show conclusively that there are fundamental differences in the regulation of dNTP biosynthesis between the cells of higher and lower eukaryotes after DNA damage.

Ort, förlag, år, upplaga, sidor
Umeå: Umeå universitet, 2006. s. 48
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1008
Nyckelord
ribonucleotide reductase, DNA damage, dNTP pools
Nationell ämneskategori
Cell- och molekylärbiologi
Identifikatorer
urn:nbn:se:umu:diva-706 (URN)91-7264-009-X (ISBN)
Disputation
2006-03-17, KB3A9, KBC, Umeå Universitet, 90187 Umeå, 09:00 (Engelska)
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Handledare
Tillgänglig från: 2006-02-23 Skapad: 2006-02-23 Senast uppdaterad: 2018-06-09Bibliografiskt granskad

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Håkansson, PelleDomkin, VladimirThelander, Lars

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