Russian Journal of GeneticsRussian Journal of GeneticsГенетика0016-67583034-5103The Russian Academy of Sciences67659210.31857/S0016675824120035waumsdГЕНЕТИКА МИКРООРГАНИЗМОВResearch ArticleThe Reparative dna Polymerase eta (Polη) Plays a key Role in Mutagenesis at Low Doses of uv Radiation in Yeast Saccharomyces cerevisiaeРепаративная ДНК-полимераза eta (Polη) играет ключевую роль в мутагенезе при низких дозах УФ-облучения у дрожжей Saccharomyces cerevisiaeAlekseevaE. A.АлексееваЕ. А.
Russian Federation
alekseeva_ea@pnpi.nrcki.ruEvstyukhinaT. A.ЕвстюхинаТ. А.
Russian Federation
alekseeva_ea@pnpi.nrcki.ruSkobelevaI. I.СкобелеваИ. И.
Russian Federation
alekseeva_ea@pnpi.nrcki.ruPeshekhonovV. T.ПешехоновВ. Т.
Russian Federation
alekseeva_ea@pnpi.nrcki.ruKorolevV. G.КоролевВ. Г.
Russian Federation
alekseeva_ea@pnpi.nrcki.ruKonstantinov Petersburg Nuclear Physics Institute of the National Research Centre “Kurchatov Institute”Петербургский институт ядерной физики им. Б.П. Константинова Национального исследовательского центра “Курчатовский институт”Kurchatov Genome Center — Petersburg Nuclear Physics InstituteКурчатовский геномный центр – ПИЯФ151220246012253503032025Copyright ©; 2024, Russian Academy of SciencesCopyright ©; 2024, Российская академия наук2024Russian Academy of SciencesРоссийская академия наукhttps://transsyst.ru/0016-6758/article/view/676592

Under normal conditions and when exposed to low doses of mutagens, DNA damage tolerance systems (DDT) are a key way to combat DNA damage in bacterial and eukaryotic cells. Two different DDT pathways, erroneous (translesion synthesis – TLS) and error-free (recombination), operate in all eukaryotic organisms. TLS involves the protein complex polymerase zeta (Polζ) (encoded by the genes REV1, REV3 and REV7), and polymerase eta (Polη) (encoded by the RAD30 gene); these polymerases are conserved from yeast to humans. We have shown that at low levels of UV radiation doses, a decisive role in mutagenesis is played by the high activity of Poly, which bypasses the overwhelming number of DNA damage that got in the way of the replication machine. Both in the case of irradiation with high and low doses of UV rays, checkpoint plays an important role in induced mutagenesis. However, the roles of genes involved in the regulation of UV-induced mutagenesis at low and high doses often differ. Inactivation of the RAD30 gene at low doses leads to an increased level of induced mutagenesis, and at high doses it practically does not differ from the level of the wild-type strain. Deletions of the HIM1, HSM3 and HIF1 genes, on the contrary, reduce the high level of mutagenesis characteristic of high doses to the level of the wild-type strain at low doses. These differences characterize the local and global checkpoint.

В нормальных условиях и при воздействии малых доз мутагенов ключевым способом борьбы с повреждениями ДНК у бактериальных и эукариотических клеток является система толерантности к повреждениям ДНК (ТПД). Две различные ветви ТПД, ошибочная (translesion synthesis – TLS) и безошибочная (рекомбинационная), функционируют во всех эукариотических организмах. TLS вовлекает белковый комплекс полимеразы дзета (Polζ) (кодируемый генами REV1, REV3 и REV7) и полимеразу эта (Polη) (кодируемую геном RAD30); эти полимеразы эволюционно консервативны от дрожжей до человека. Мы показали, что при низких уровнях доз УФ-излучения решающую роль в мутагенезе играет высокая активность Polη, которая обходит подавляющее число оказавшихся на пути репликативной машины повреждений ДНК. Как в случае облучения высокими, так и низкими дозами УФ-лучей большую роль в индуцированном мутагенезе играет чекпойнт. Однако функции генов, участвующих в регуляции УФ-индуцированного мутагенеза при низких и высоких дозах, часто различаются. Инактивация гена RAD30 при низких дозах приводит к повышенному уровню индуцированного мутагенеза, а при высоких дозах мутагенез практически не отличается от уровня штамма дикого типа. Делеции генов HIM1, HSM3 и HIF1, наоборот, снижают высокий уровень мутагенеза, характерный для высоких доз, до уровня штамма дикого типа при низких дозах. Эти различия, по-видимому, характеризуют локальный и глобальный чекпойнт.

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