Compartimentation et dynamique des fonctions nucléaires

Publications de l’équipe

Année de publication : 2020

Judith Miné-hattab, Irène Chiolo (2020 Aug 27)

Complex Chromatin Motions for DNA Repair

Frontiers in Genetics : DOI : https://doi.org/10.3389/fgene.2020.00800 En savoir plus
Résumé

A number of studies across different model systems revealed that chromatin undergoes significant changes in dynamics in response to DNA damage. These include local motion changes at damage sites, increased nuclear exploration of both damaged and undamaged loci, and directed motions to new nuclear locations associated with certain repair pathways. These studies also revealed the need for new analytical methods to identify directed motions in a context of mixed trajectories, and the importance of investigating nuclear dynamics over different time scales to identify diffusion regimes. Here we provide an overview of the current understanding of this field, including imaging and analytical methods developed to investigate nuclear dynamics in different contexts. These dynamics are essential for genome integrity. Identifying the molecular mechanisms responsible for these movements is key to understanding how their misregulation contributes to cancer and other genome instability disorders.

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Myriam Ruault, Vittore F. Scolari, Luciana Lazar-Stefanita, Antoine Hocher, Isabelle Loïodice, Camille Noûs, Romain Koszul, Angela Taddei (2020 Jun 29)

The silencing factor Sir3 is a molecular bridge that sticks together distant loci

preprint- : DOI : 10.1101/2020.06.29.178368 En savoir plus
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Judith Miné-Hattab*, Mathias Heltberg, Marie Villemeur, Chloé Guedj, Thierry Mora, Aleksandra M. Walczak, Maxime Dahan, Angela Taddei*, co-corresponding authors (2020 Jun 19)

Single molecule microscopy reveals key physical features of repair foci in living cells

preprint- : DOI : 10.1101/2020.06.18.160085 En savoir plus
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HOCHER Antoine, TADDEI Angela (2020 Mar 17)

Subtelomeres as Specialized Chromatin Domains

Bioessaysreview : 42 (5) : DOI : 10.1002/bies.201900205 En savoir plus
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Année de publication : 2019

Garance Alberman, Jean-Marie Gagez, Judith Miné-Hattab (2019 Dec 18)

[When science and music meet].

Medecine sciences : M/S : 881-885 : DOI : 10.1051/medsci/2019169 En savoir plus
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Elie Dolgin (2019 May 7)

The sounds of science: biochemistry and the cosmos inspire new music

Nature- : DOI : 10.1038/d41586-019-01422-0 En savoir plus
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Judith Miné-Hattab, Angela Taddei (2019 Apr 1)

Physical principles and functional consequences of nuclear compartmentalization in budding yeast.

Current opinion in cell biology : 105-113 : DOI : 10.1016/j.ceb.2019.02.005 En savoir plus
Résumé

One striking feature of eukaryotic nuclei is the existence of discrete regions, in which specific factors concentrate while others are excluded, thus forming microenvironments with different molecular compositions and biological functions. These domains are often referred to as subcompartments even though they are not membrane enclosed. Despite their functional importance the physical nature of these structures remains largely unknown. Here, we describe how the Saccharomyces cerevisiae nucleus is compartmentalized and discuss possible physical models underlying the formation and maintenance of chromatin associated subcompartments. Focusing on three particular examples, the nucleolus, silencing foci, and repair foci, we discuss the biological implications of these different models as well as possible approaches to challenge them in living cells.

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Klein et al. (2019 Jan 7)

Guidelines for DNA recombination and repair studies: Cellular assays of DNA repair pathways

Microb Cell- : DOI : 10.15698/mic2019.01.664 En savoir plus
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Année de publication : 2018

Judith Miné-Hattab, Xavier Darzacq (2018 Nov 20)

[Chromatin mobility upon DNA damage: a multi-scale story].

Medecine sciences : M/S : 778-781 : DOI : 10.1051/medsci/2018214 En savoir plus
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Antoine Hocher, Myriam Ruault, Petra Kaferle, Marc Descrimes, Mickaël Garnier, Antonin Morillon, Angela Taddei (2018 Oct 26)

Expanding heterochromatin reveals discrete subtelomeric domains delimited by chromatin landscape transitions.

Genome research : DOI : gr.236554.118 En savoir plus
Résumé

The eukaryotic genome is divided into chromosomal domains of heterochromatin and euchromatin. Transcriptionally silent heterochromatin is found at subtelomeric regions, leading to the telomeric position effect (TPE) in yeast fly and human. Heterochromatin generally initiates and spreads from defined loci, and diverse mechanisms prevent the ectopic spread of heterochromatin into euchromatin. Here, we overexpressed the silencing factor Sir3 at varying levels in yeast and found that Sir3 spreads into Extended Silent Domains (ESDs), eventually reaching saturation at subtelomeres. We observed the spread of Sir3 into subtelomeric domains associated with specific histone marks in wild-type cells and stopping at zones of histone mark transitions including H3K79 tri-methylation levels. Our study shows that the conserved H3K79 methyltransferase Dot1 is essential in restricting Sir3 spread beyond ESDs, thus ensuring viability upon overexpression of Sir3. Lastly, our analyses of published data demonstrate how ESDs unveil uncharacterized discrete domains isolating structural and functional subtelomeric features from the rest of the genome. Our work offers a new approach on how to separate subtelomeres from the core chromosome.

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Année de publication : 2017

Judith Miné-Hattab, Vincent Recamier, Ignacio Izeddin, Rodney Rothstein, Xavier Darzacq (2017 Aug 11)

Multi-scale tracking reveals scale-dependent chromatin dynamics after DNA damage.

Molecular biology of the cell : DOI : mbc.E17-05-0317 En savoir plus
Résumé

The dynamic organization of genes inside the nucleus is an important determinant for their function. Using fast DNA tracking microscopy in cells and improved analysis of mean square displacements, we quantified DNA motion at time scales ranging from 10 milliseconds to minute and found that following DNA damage, DNA exhibits distinct sub-diffusive regimes. In response to double-strand breaks, chromatin is more mobile at large time scales but, surprisingly, its mobility is reduced at short time scales. This effect is even more pronounced at the site of damage. Such a pattern of dynamics is consistent with a global increase in chromatin persistence length in response to DNA damage. Scale-dependent nuclear exploration is regulated by the Rad51 repair protein, both at the break and throughout the genome. We propose a model in which stiffening of the damaged ends by the repair complex, combined with global increased stiffness, act like a « needle in a ball of yarn », enhancing the ability of the break to traverse the chromatin meshwork.

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Amandine Batté, Clémentine Brocas, Hélène Bordelet, Antoine Hocher, Myriam Ruault, Adouda Adjiri, Angela Taddei, Karine Dubrana (2017 Jul 30)

Recombination at subtelomeres is regulated by physical distance, double-strand break resection and chromatin status.

The EMBO journal : 2609-2625 : DOI : 10.15252/embj.201796631 En savoir plus
Résumé

Homologous recombination (HR) is a conserved mechanism that repairs broken chromosomes via intact homologous sequences. How different genomic, chromatin and subnuclear contexts influence HR efficiency and outcome is poorly understood. We developed an assay to assess HR outcome by gene conversion (GC) and break-induced replication (BIR), and discovered that subtelomeric double-stranded breaks (DSBs) are preferentially repaired by BIR despite the presence of flanking homologous sequences. Overexpression of a silencing-deficient SIR3 mutant led to active grouping of telomeres and specifically increased the GC efficiency between subtelomeres. Thus, physical distance limits GC at subtelomeres. However, the repair efficiency between reciprocal intrachromosomal and subtelomeric sequences varies up to 15-fold, depending on the location of the DSB, indicating that spatial proximity is not the only limiting factor for HR EXO1 deletion limited the resection at subtelomeric DSBs and improved GC efficiency. The presence of repressive chromatin at subtelomeric DSBs also favoured recombination, by counteracting EXO1-mediated resection. Thus, repressive chromatin promotes HR at subtelomeric DSBs by limiting DSB resection and protecting against genetic information loss.

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Eldad Kepten, Judith Miné-Hattab (2017 Feb 28)

[Lamin A: a key protein in chromatin motion].

Medecine sciences : M/S : 126-130 : DOI : 10.1051/medsci/20173302004 En savoir plus
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Année de publication : 2015

Ivaylo Nikolov, Angela Taddei (2015 Oct 30)

Linking replication stress with heterochromatin formation.

Chromosoma : 523-33 : DOI : 10.1007/s00412-015-0545-6 En savoir plus
Résumé

The eukaryotic genome can be roughly divided into euchromatin and heterochromatin domains that are structurally and functionally distinct. Heterochromatin is characterized by its high compaction that impedes DNA transactions such as gene transcription, replication, or recombination. Beyond its role in regulating DNA accessibility, heterochromatin plays essential roles in nuclear architecture, chromosome segregation, and genome stability. The formation of heterochromatin involves special histone modifications and the recruitment and spreading of silencing complexes that impact the higher-order structures of chromatin; however, its molecular nature varies between different chromosomal regions and between species. Although heterochromatin has been extensively characterized, its formation and maintenance throughout the cell cycle are not yet fully understood. The biggest challenge for the faithful transmission of chromatin domains is the destabilization of chromatin structures followed by their reassembly on a novel DNA template during genomic replication. This destabilizing event also provides a window of opportunity for the de novo establishment of heterochromatin. In recent years, it has become clear that different types of obstacles such as tight protein-DNA complexes, highly transcribed genes, and secondary DNA structures could impede the normal progression of the replisome and thus have the potential to endanger the integrity of the genome. Multiple studies carried out in different model organisms have demonstrated the capacity of such replisome impediments to favor the formation of heterochromatin. Our review summarizes these reports and discusses the potential role of replication stress in the formation and maintenance of heterochromatin and the role that silencing proteins could play at sites where the integrity of the genome is compromised.

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Micol Guidi, Myriam Ruault, Martial Marbouty, Isabelle Loïodice, Axel Cournac, Cyrille Billaudeau, Antoine Hocher, Julien Mozziconacci, Romain Koszul, Angela Taddei (2015 Apr 2)

Spatial reorganization of telomeres in long-lived quiescent cells.

Genome biology : 206 : DOI : 10.1186/s13059-015-0766-2 En savoir plus
Résumé

The spatiotemporal behavior of chromatin is an important control mechanism of genomic function. Studies in Saccharomyces cerevisiae have broadly contributed to demonstrate the functional importance of nuclear organization. Although in the wild yeast survival depends on their ability to withstand adverse conditions, most of these studies were conducted on cells undergoing exponential growth. In these conditions, as in most eukaryotic cells, silent chromatin that is mainly found at the 32 telomeres accumulates at the nuclear envelope, forming three to five foci.

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