Alternative splicing at exon 2 results in the loss of the catalytic activity of mouse DNA polymerase iota in vitro
| Autor: | L. V. Gening, Konstantin Y. Kazachenko, Alena V. Makarova, Nataliya Miropolskaya, Vyacheslav Z. Tarantul |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
DNA Replication
0301 basic medicine DNA Repair DNA polymerase DNA repair viruses DNA-Directed DNA Polymerase Biochemistry Mice 03 medical and health sciences Exon Catalytic Domain Animals Amino Acid Sequence Molecular Biology Sequence Deletion biology Alternative splicing DNA replication Exons Cell Biology Processivity Base excision repair Molecular biology Alternative Splicing 030104 developmental biology DNA Polymerase iota biology.protein DNA Polymerase Iota Sequence Alignment |
| Zdroj: | DNA Repair. 50:77-82 |
| ISSN: | 1568-7864 |
| Popis: | Y-family DNA polymerase iota (Pol ι) possesses both DNA polymerase and dRP lyase activities and was suggested to be involved in DNA translesion synthesis and base excision repair in mammals. The 129 strain of mice and its derivatives have a natural nonsense codon mutation in the second exon of the Pol ι gene resulting in truncation of the Pol ι protein. These mice were widely used as a Pol ι-null model for in vivo studies of the Pol ι function. However whether 129-derived strains of mice are fully deficient in the Pol ι functions was a subject of discussion since Pol ι mRNA undergoes alternative splicing at exon 2. Here we report purification of mouse Pol ι lacking the region encoded by exon 2, which includes several conserved residues involved in catalysis. We show that the deletion abrogates both the DNA polymerase and dRP lyase activities of Pol ι in the presence of either Mg2+ or Mn2+ ions. Thus, 129-derived strains of mice express catalytically inactive alternatively spliced Pol ι variant, whose cellular functions, if any exist, remain to be established. |
| Databáze: | OpenAIRE |
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