REPLI-HEM · Mechanisms promoting the formation and migration of cruciform sister chromatid junctions during chromosome replication
6РП — Действия „Мария Кюри“
- Период
- 2006-07-01 → 2008-06-30
- Финансиране от ЕС
- 143 746 €
- Участници
- 1
- Схема
- EIF
Линиите свързват координатора с партньорите.
Накратко на български
Протеините HMO1 и SGS1 при дрождите регулират стабилността на ДНК по време на копирането на хромозомите. Разбирането на тези механизми помага да се разбере как се възникват генетични грешки, които могат да доведат до развитие на рак при хората.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - REPLI-HEM (Mechanisms promoting the formation and migration of cruciform sister chromatid junctions during chromosome replication.)
We have used the budding yeast Saccharomyces cerevisiae as a model system to study factors influencing genome stability. The maintenance of genome integrity is pivotal to prevent cancer. Chromosomal rearrangements can result from unrepaired DNA lesions or from aberrant DNA repair events, often associated with recombination. We have studied the role of a series of proteins involved in the metabolism of recombination structures arising during chromosome replication. In particular we have extensively characterised the yeast protein HMO1 that belongs to the high mobility group (HMG) family of proteins; mutations in the human orthologs of this protein have been found in several tumour types. We have found that HMO1 is involved in the formation and/or stabilisation of certain recombinogenic structures which are resolved by SGS1, a member of the RecQ helicase family. Mutations in human orthologs of SGS1, BLM and WRN helicases, cause the cancer-prone Bloom and Werner syndromes; in addition we also found a possible regulation of HMO1 DNA binding through sumoylation. We also found that deletion of HMO1 results in a delayed and weakened activation of checkpoint; whether this is due to a direct participation of HMO1 in the checkpoint signalling cascade or to an indirect effect is still to be elucidated. These results altogether allow us to envisage a scenario in which HMO1 would work in the response to DNA damage at two levels, maybe related among them. First, by ensuring an efficient activation of the checkpoint response. Second, facilitating chromosome replication across DNA lesions.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Eukaryotic cells replicate their genome by firing multiple replicons throughout the S phase of the cell cycle. Origin firing is a highly controlled process and is coupled with the formation of specialized cruciform junctions. These structures have been con served throughout evolution and likely contribute to the establishment of sister chromatid cohesion during S phase and to assist sister chromatid-mediated replication and recombination processes. Under pathological situations these sister chromatid junctions (SCJs) represent a source of DNA damage as they can be converted into reversed forks in the absence of a functional checkpoint or into recombination structures in cells defective in RecQ helicases. SCJs form at an early step of DNA synthesis and chase replication forks although the mechanims leading to their formation and migration remain elusive. M. Foiani and collaborators have extensively characterized the SCJs that form during replication in budding yeast both under physiological and pathological situation. The aim of the present proposal is to understand at the mechanistic level how these structures form during initiation of DNA synthesis and how they move through the replicon chasing replication forks.
Оригинален текст от CORDIS (на английски).
Участници
- IFOM FONDAZIONE ISTITUTO FIRC DI ONCOLOGIA MOLECOLARE · MILANКоординаторИталия
Връзки
Данни: CORDIS, © Европейски съюз