Russian Journal of GeneticsRussian Journal of GeneticsГенетика0016-67583034-5103The Russian Academy of Sciences66722710.31857/S0016675824070023BILQZPГЕНЕТИКА МИКРООРГАНИЗМОВResearch ArticleThe role of different subunits of INO80 remodeling complex in repair chromatin assembly in yeast Saccharomyces cerevisiaeРоль различных субъединиц ремоделирующего комплекса INO80 в репарационной сборке хроматина у дрожжей Saccharomyces cerevisiaeEvstyukhinaT. А.ЕвстюхинаТ. А.
Russian Federation
alekseeva_ea@pnpi.nrcki.ruAlekseevaE. A.АлексееваЕ. 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.ruPetersburg Nuclear Physics Institute Named by B.P. Konstantinov of 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 – ПИЯФ15072024607173026022025Copyright ©; 2024, Russian Academy of SciencesCopyright ©; 2024, Российская академия наук2024Russian Academy of SciencesРоссийская академия наукhttps://transsyst.ru/0016-6758/article/view/667227

Reparative chromatin assembly is an important step in maintaining genome stability. The correct assembly of chromatin is provided by histone chaperones, whose dysfunction can lead to the development of various forms of cancer and a number of hereditary diseases in humans. The effect of remodeling factors completes chromatin repair. The yeast chromatin remodeling complex INO80 plays an important role in chromatin architecture. We used induced mutagenesis and real-time PCR to study the role of INO80 in chromatin repair assembly. In double mutants ies5Δ hsm3Δ(hif1Δ), defects in the structure of nucleosomes caused by mutations hsm3Δ and hif1Δ lead to hypersensitivity of cells to UV radiation and the disappearance of hsm3- and hif1-specific mutagenesis. Double mutants carrying the nhp10Δ mutation and hsm3Δ or hif1Δ mutations were indistinguishable from a single mutant in terms of the lethal effect of UV irradiation, however, the high UV-induced mutagenesis characteristic of all mutations disappeared. Thus, we found that mutations in the genes controlling the subunits of the INO80 complex can exhibit strong interactions with mutations in histone chaperone genes. We have confirmed the hypothesis that the Him1 protein performs a chaperone function in the process of reparative chromatin assembly.

Репаративная сборка хроматина является важным шагом в поддержании стабильности генома. Правильную сборку хроматина обеспечивают шапероны гистонов, нарушение функции которых может привести к развитию различных форм рака и к ряду наследственных заболеваний у человека. Действие факторов ремоделирования завершает репарацию хроматина. Ремоделирующий комплекс хроматина дрожжей INO80 играет важную роль в архитектуре хроматина. Мы использовали индуцированный мутагенез и ПЦР в реальном времени для изучения роли INO80 в репарационной сборке хроматина. У двойных мутантов ies5Δ hsm3Δ (hif1Δ) дефекты структуры нуклеосом, вызванные мутациями hsm3Δ и hif1Δ, приводят к гиперчувствительности клеток к УФ-облучению и исчезновению hsm3- и hif1-специфического мутагенеза. Двойные мутанты, несущие мутацию nhp10Δ и мутацию hsm3Δ или hif1Δ, были неотличимы от одиночного мутанта по летальному эффекту УФ-облучения, однако высокий УФ-индуцированный мутагенез, характерный для всех мутаций, исчезал. Таким образом, мы обнаружили, что мутации в генах, контролирующих субъединицы комплекса INO80, могут проявлять сильные взаимодействия с мутациями в генах гистоновых шаперонов. Была подтверждена гипотеза о том, что белок Him1 выполняет шаперонную функцию в процессе репаративной сборки хроматина.

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