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Quaternary structure of the human Cdt1-Geminin complex regulates DNA replication licensingстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 3 декабря 2017 г.
- Авторы: De Marco V., Gillespie P.J., Li A., Karantzelis N., Christodoulou E., Klompmaker R., van Gerwen S., Fish A., Petoukhov M.V., Iliou M.S., Lygerou Z., Medema R.H., Blow J.J., Svergun D.I., Taraviras S., Perrakis A.
- Журнал: Proceedings of the National Academy of Sciences of the United States of America
- Том: 106
- Номер: 47
- Год издания: 2009
- Издательство: National Academy of Sciences
- Местоположение издательства: United States
- Первая страница: 19807
- Последняя страница: 19812
- DOI: 10.1073/pnas.0905281106
- Аннотация: All organisms need to ensure that no DNA segments are rereplicated in a single cell cycle. Eukaryotes achieve this through a process called origin licensing, which involves tight spatiotemporal control of the assembly of prereplicative complexes (pre-RCs) onto chromatin. Cdt1 is a key component and crucial regulator of pre-RC assembly. In higher eukaryotes, timely inhibition of Cdt1 by Geminin is essential to prevent DNA rereplication. Here, we address the mechanism of DNA licensing inhibition by Geminin, by combining X-ray crystallography, small-angle X-ray scattering, and functional studies in Xenopus and mammalian cells. Our findings show that the Cdt1: Geminin complex can exist in two distinct forms, a “permissive” heterotrimer and an “inhibitory” heterohexamer. Specific Cdt1 residues, buried in the heterohexamer, are important for licensing. We postulate that the transition between the heterotrimer and the heterohexamer represents a molecular switch between licensing-competent and licensing-defective states.
- Добавил в систему: Петухов Максим Владимирович