H2020Индивидуална стипендия2022–2024

DIRECT-DSB · Dissecting the role of transcription in meiotic DNA double-strand breaks patterning

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2022-05-01 → 2024-10-31
Финансиране от ЕС: 196 708 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Ролята на транскрипцията при разпределението на счупванията в ДНК се изучава чрез едноклетъчния организъм Tetrahymena thermophila. Това помага за по-доброто разбиране на молекулярните процеси при мейозата, чиито дефекти могат да доведат до безплодие или вродени дефекти като синдрома на Даун.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Dissecting the role of transcription in meiotic DNA double-strand breaks patterning

Meiosis is a unique cell division process that generates gametes, and defects in meiosis often lead to infertility or birth defects, such as Down syndrome. Successful meiosis requires the formation of hundreds of DNA double-strand breaks (DSBs) at specific chromatin sites. These DSB patterns are believed to be regulated by certain chromatin features established during transcription. However, because transcription is vital for cellular function, studying its influence on DSB patterning during meiosis in conventional model organisms is challenging. Tetrahymena thermophila, a unicellular protist with two nuclei, provides a solution. Since all its protein-coding mRNAs are generated from its somatic nucleus, transcription can be halted in its meiotic nucleus without disrupting meiotic progression. Hence, the DIRECT-DSB project was initiated to exploit this unique feature, aiming to examine transcription's role in DSB patterning without the limitations faced in other model organisms. By characterizing and comparing DSB patterns and chromatin features in the presence and absence of transcription, a mutually exclusive relationship between DSB formation and transcription was uncovered. This finding provides a deeper understanding of how meiotic processes are regulated at the molecular level. It highlights the potential role of transcription in negatively influencing DSB patterns in Tetrahymena, which are crucial for the accurate segregation of chromosomes. Meanwhile, innovative techniques established during the implementation of this project facilitated using Tetrahymena as a model for the dissection of complex processes in ways that are not possible in other systems, potentially leading to broader discoveries in genetics and cell biology.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Meiosis is a specialized cell division process for producing gametes, and meiotic defects frequently cause infertility or birth defects (e.g. Down syndrome). Successful meiosis is ensured by the induction of hundreds of DNA double-strand breaks (DSBs) at the correct chromatin sites. The pattern of DSBs is suggested to be controlled by some special chromatin features that are established upon transcription. However, as transcription is essential for life, it is difficult to directly study whether and how transcription influences DSB patterning during meiosis in common model organisms.The unicellular protist Tetrahymena thermophila has two nuclei and, importantly, transcription can be shut off in the meiotic nucleus without affecting meiotic progression. Therefore, the DIRECT-DSB project was designed to overcome the intrinsic limitations of other model systems by investigating the impact of transcription on DSB patterning in Tetrahymena.Through in-depth collaborations with the host supervisor, who has a profound knowledge of chromatin biology, and with other leading researchers with expertise in meiosis, I will first characterize and compare DSB patterns and chromatin features in the presence and absence of transcription and then study potential correlations between DSB pattern alterations and transcription-induced chromatin alterations. The successful accomplishment of the project will (i) clarify the relationship between transcription and DSB patterning, which has been a much-debated topic in the meiosis field for many years; (ii) deepen our understanding of meiosis, which, in the longer term, may contribute to solving the problem of increasing infertility rates in the European Union and elsewhere; (iii) enable knowledge exchange and dissemination, and the establishment of novel methods; and (iv) help me to develop into a leading independent scholar by improving my research proficiency and transferable skills.

Оригинален текст от CORDIS (на английски).

Участници

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS · ParisКоординаторФранция