A False Note of DNA Polymerase Iota in the Choir of Genome Caretakers in Mammals

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L. V. Gening¹, A. V. Makarova¹, A. M. Malashenko², and V. Z. Tarantul^1*

¹Institute of Molecular Genetics, Russian Academy of Sciences, pl. Kurchatova 2, 123182 Moscow, Russia; fax: (7-495) 196-0221; E-mail: tarantul@img.ras.ru

²Research Laboratory for Experimental Biological Models, Russian Academy of Medical Sciences, 143440 Svetlye Gory, Moscow Region, Russia

^* To whom correspondence should be addressed.

Received July 22, 2005; Revision received September 6, 2005

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DNA polymerase iota (Poliota) 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 Poliota 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 Poliota. We measured the enzyme activity of Poliota 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 Poliota 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 poliota gene, the Poliota 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 poliota gene. This supports tissue-specific regulation of poliota gene expression through alternative splicing. A semiquantitative determination of Poliota activity in mice strains different in their radiosensitivity suggests a reciprocal correlation between the enzyme activity of Poliota in testis and the resistance of mice to radiation.

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KEY WORDS: DNA polymerase iota, genome caretakers, mouse strains, brain, testis, sensitivity to radiation

DOI: 10.1134/S0006297906020064

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