Генетические элементы особого типа

В частности, может происходить транслокация между 8-й и 22-й хромосомами; последняя содержит гены легких Х-цепей иммуноглобулинов. Подобная транслокация имеет место также между 8-й и 2-й хромосомами; 2-я хромосома несет гены легких х-цепей. Как показал Кроче в сотрудничестве с Ноуэллом, а также Г. Ленуаром из Международного агентства раковых исследований в Лионе, в обоих случаях ген с-тус остается в составе 8-й хромосомы, но к нему присоединяется последовательность ДНК, ответственная за образование антител (в первом случае это локус легких Х-цепей, а во втором — *-цепей). И при той, и при другой транслокации онкоген может активироваться, становясь невосприимчивым к механизмам, регулирующим его экспрессию в норме. Видимо, для усиленной экспрессии онкогена с- тус его перемещение не обязательно.

КАКОВА причина нарушения регуляции онкогена с-тус, происходящего при описанных выше транслоканиях? Ответ на этот вопрос подсказал эксперимент, в котором наблюдалось, что транслоцированный онкоген с-тус лимфомы Беркитта репрессирован в гибридных клетках, полученных из фибробластов мыши (клеток соединительной ткани), но активно транскрибируется в гибридных клетках, полученных на основе клеток плазмацитомы (раковых клеток, продуцирующих антитела). Таким образом, оказывается, что транслокация имеет онкогенный эффект только в клетках, синтезирующих антитела, т.е. в тех клетках, где участки хромосом, необходимые для образования иммуноглобулинов, функционируют особенно активно.

Такие участки хромосом содержат генетические элементы особого типа — усилители транскрипции. Это последовательности ДНК, которые, по-видимому, усиливают эффективность транскрипции определенных генов той хромосомы, в которой они локализованы; они были обнаружены недавно, и о механизме их функционирования известно мало. Группа К. Ка- лейм в Калифорнийском университете в Лос-Анджелесе, У. Шаффнер с сотрудниками в Цюрихском университете, а также С. Тонегава и его коллеги в Массачусетском технологическом институте (МТИ) выявили усилители транскрипции в составе участка ДНК, который кодирует один из вариантов константной области тяжелых цепей иммуноглобулинов. Недавние исследования, проведенные в Вистаровском институте, позволяют предполагать, что в локусе тяжелых цепей имеются дополнительные усилители транскрипции. Кроме того, Д. Балтимор и его сотрудники в МТИ обнаружили усилители транскрипции в участке хромосомы, кодирующем константную область легких v-цепей.

 

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