EIF-SMC5/6 COMPLEX · Investigating the role of the Smc5/6 complex during DNA replication and repair of DNA.
6РП — Действия „Мария Кюри“
- Период
- 2006-01-01 → 2007-12-31
- Финансиране от ЕС
- 159 046 €
- Участници
- 1
- Схема
- EIF
Линиите свързват координатора с партньорите. За проекти отпреди 2014 г. CORDIS не винаги дава точни координати. Тези точки са на ниво град или държава.
Накратко на български
Комплексът Smc5/6 се изследва в контекста на поправката на счупените нишки на ДНК, например при грешки по време на репликацията. Това помага да се разбере как се поддържа стабилността на генома и се предотвратява развитието на рак.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - EIF-SMC5/6 COMPLEX (Investigating the role of the Smc5/6 complex during DNA replication and repair of DNA.)
DNA double-strand breaks (DSB) are one of the most common and threatening alterations of a cell's genetic material. Left unrepaired, DSBs can cause cell death and, if misrepaired, they can lead to genomic instability and the development of cancer in multicellular organisms. DNA double-strand breaks can occur during DNA replication or after DNA damage. The Smc5-Smc6 complex was initially discovered through a genetic screen looking for radiation-sensitive mutants in fission yeast (Structural maintenance of chromosomes = SMC). The Smc5-Smc6 complex is conserved from yeast to human and in yeast all subunits are essential. The complex is involved in DNA repair and is required for the stability of the repetitive ribosomal gene cluster in budding yeast. In my project I could demonstrate that following a single DSB induced by the HO endonuclease system, Smc5-Smc6 subunits are recruited to the vicinity of the break de novo. Physical analysis of the repair of induced DSBs in smc5-smc6 mutants reveals that inactivation of the complex reduces sister chromatid recombination (SCR). I could also show that Smc5-Smc6 do not significantly contribute to the religation of a DSB by the 'non-homologous end joining' (NHEJ) repair pathway. These findings demonstrate that the Smc5-Smc6 complex is essential to maintain genome stability because it directs repair of replication-induced DSBs through error-free sister chromatid recombination pathways, thus suppressing inappropriate non-sister recombination events.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Faithful DNA replication and repair of DNA damage are required for genome stability and contribute to the health and survival of all organisms. Checkpoint pathways modulate DNA replication during normal cell cycles and during DNA damage repair, but little is known about the genetic and molecular determinants. The genome cycle requires DNA to be organised and manipulated, during replication, mitosis and repair. Eukaryotic genomes contain six highly conserved SMC proteins forming three types of heterodimers, which are the core of distinct multiprotein complexes involved in different aspects of DNA metabolism, including chromosome condensation and sister chromatid cohesion (Nasmyth, 2001). The Smc5/6 complex has been thought to be involved in DNA repair (Lehman n et al., 1995). However, all subunits of the complex are essential even in the absence of extrinsic DNA damage, demonstrating that this complex must have additional uncharacterised roles during some aspect of DNA metabolism. Recent studies have raised the possibility that the complex is involved in replication fork biology. The proposed research plan is aimed at testing the hypothesis that the Smc5/6 complex is directly involved in the stability of replication forks during unperturbed cell cycles and in re sponse to the DNA damaging agent hydroxyurea. To this end, I have conceived a multidisciplinary research approach that combines genetics, biochemistry and cytology in S. cerevisiae to investigate the function of this protein complex at replication forks. P rocesses related to replication fork stalling or collapse are, unsurprisingly, essential for the maintenance of genomic integrity and for the prevention of tumorigenesis. The proposed research will contribute to the understanding of genome stability and th us could ultimately be exploited to treat cancer.
Оригинален текст от CORDIS (на английски).
Участници
- CLINICAL SCIENCE CENTRE, MEDICAL RESEARCH COUNCIL · LONDONКоординаторНиво граднепознат регион
Връзки
Данни: CORDIS, © Европейски съюз