A false note of DNA polymerase iota in the choir of genome caretakers in mammals

Biochemistry (Mosc). 2006 Feb;71(2):155-9. doi: 10.1134/s0006297906020064.

Abstract

DNA polymerase iota (Pol iota) of mammals is a member of the Y family of DNA polymerases. Among many other genome caretakers, these enzymes are responsible for maintaining genome stability. The members of the Y-family DNA polymerases take part in translesion DNA synthesis, bypassing some DNA lesions, and are characterized by low fidelity of DNA synthesis. A unique ability of Pol iota to predominantly incorporate G opposite T allowed us to identify the product of this enzyme among those synthesized by other DNA polymerases. This product can be called a "false note" of Pol iota. We measured the enzyme activity of Pol iota in crude extracts of cells from different organs of five inbred strains of mice (N3H/Sn, 101/H, C57BL/6, BALB/c, 129/J) that differed in a number of parameters. The "false note" of Pol iota was clearly sounding only in the extracts of testis and brain cells from four analyzed strains: N3H/Sn, 101/H, C57BL/6, BALB/c. In mice of 129/J strain that had a nonsense mutation in the second exon of the pol iota gene, the Pol iota activity was reliably detectable only in the extracts of brain. The data show that the active enzyme can be formed in some cell types even if they carry a nonsense mutation in the pol iota gene. This supports tissue-specific regulation of pol iota gene expression through alternative splicing. A semiquantitative determination of pol iota activity in mice strains different in their radiosensitivity suggests a reciprocal correlation between the enzyme activity of pol iota in testis and the resistance of mice to radiation.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Brain / enzymology
  • Catalytic Domain
  • Codon, Nonsense / chemistry*
  • Codon, Nonsense / metabolism*
  • DNA Replication / genetics
  • DNA-Directed DNA Polymerase / chemistry*
  • DNA-Directed DNA Polymerase / genetics*
  • DNA-Directed DNA Polymerase / metabolism
  • Genomic Instability*
  • Guanine / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Nucleic Acid Synthesis Inhibitors
  • Organ Specificity / genetics
  • Testis / enzymology
  • Testis / radiation effects
  • Thymine / metabolism

Substances

  • Codon, Nonsense
  • Nucleic Acid Synthesis Inhibitors
  • Guanine
  • DNA polymerase iota
  • DNA-Directed DNA Polymerase
  • Thymine