РОЛЬ ТИМИН ДНК-ГЛИКОЗИЛАЗЫ ЧЕЛОВЕКА В ЭПИГЕНЕТИЧЕСКОЙ РЕГУЛЯЦИИ ТРАНСКРИПЦИИ И СТАБИЛЬНОСТИ ГЕНОМА
DOI:
https://doi.org/10.26577/eb.2023.v97.i4.01Ключевые слова:
Тимин ДНК-гликозилаза, репарация ДНК, деметилирование ДНК, раковые заболеванияАннотация
Тимин ДНК-гликозилаза (TDG) привлекла к себе внимание благодаря своей способности удалять тимин, т.е. нормальное основание ДНК, из G:T неправильных пар. Это указывало на его функцию в эксцизионной репарации оснований ДНК в восстановлении пар оснований G:C после дезаминирования 5-метилцитозина. Из-за очевидной каталитической неэффективности, некоторые считали TDG плохим ферментом репарации ДНК без важной биологической функции. Однако было продемонстрировано, что этот фермент может действовать как ключевой игрок в транскрипционной регуляции через взаимодействие с различными ядерными рецепторами и факторами транскрипции что указывает на ее функцию в регуляции генов, которая, по-видимому, имеет решающее значение в процессах развития. Другие показали, что TDG участвует в эпигенетической регуляции экспрессии генов защищая CpG-богатые промоторы от de novo ДНК метилирования и может инициировать аберрантную репарацию. Недавние исследования на животных выявили связь между потерей TDG и началом и началом опухолеобразования. Таким образом целью данного обзора является собрать воедино результаты различных экспериментов, в которых исследовалась тимин ДНК-гликозилаза с момента ее открытия, и оценить их влияние ля определения возможных физиологических ролей этого фермента.
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