Chromatin Movement in the Maintenance of Genome Stability

Dion, Vincent; Gasser, Susan M.

doi:10.1016/j.cell.2013.02.010

Cited by 205 publications

(201 citation statements)

References 84 publications

(159 reference statements)

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“…2 and supplementary material Movies 1 and 2). In untreated cells, the average diffusion time was 99611 nm 2 /s, similar to previous reports (Dion and Gasser, 2013;Miné-Hattab and Rothstein, 2013). Fixation with formaldehyde reduced diffusion by .30-fold, indicating a modest contribution of noise to the measurements ( Fig.…”

Section: Resultssupporting

confidence: 71%

“…PPT MSD curves had plateau shapes characteristic of constrained random walk expected for chromatin (Dion and Gasser, 2013). In contrast, SPT curves had exponential shapes characteristic of directional cellular motions (supplementary material Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Homologous recombination is the major repair mechanism in yeast, whereas mammalian cells mostly use NHEJ. Recent studies in yeast have revealed increased chromosome movement after DNA cleavage Miné-Hattab and Rothstein, 2012), which might facilitate homology search during homologous recombination (Dion and Gasser, 2013). Conversely, it is expected that for NHEJ, chromatin movements might increase the frequency of genomic translocation and reduce the rate of reannealing -except under specific circumstances that necessitate long-range DNA end-joining, for example during V(D)J recombination (Difilippantonio et al, 2008).…”

Section: Tools and Techniquesmentioning

confidence: 99%

“…Studies on chromatin dynamics often rely on Lac arrays stably integrated at specific loci and visualized with fluorescent proteins (Marshall et al, 1997;Chubb et al, 2002;Dion and Gasser, 2013;Miné-Hattab and Rothstein, 2013). Some cell types such as stem or primary cells, however, cannot easily be engineered with DNA arrays and one cannot exclude that large insertions of repetitive ectopic DNA might alter chromatin behavior.…”

Section: Introductionmentioning

confidence: 99%

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Nanoscale histone localization in live cells reveals reduced chromatin mobility in response to DNA damage

Liu

Vidi

Lelièvre

et al. 2014

Journal of Cell Science

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BSTRACTNuclear functions including gene expression, DNA replication and genome maintenance intimately rely on dynamic changes in chromatin organization. The movements of chromatin fibers might play important roles in the regulation of these fundamental processes, yet the mechanisms controlling chromatin mobility are poorly understood owing to methodological limitations for the assessment of chromatin movements. Here, we present a facile and quantitative technique that relies on photoactivation of GFPtagged histones and paired-particle tracking to measure chromatin mobility in live cells. We validate the method by comparing live cells to ATP-depleted cells and show that chromatin movements in mammalian cells are predominantly energy dependent. We also find that chromatin diffusion decreases in response to DNA breaks induced by a genotoxic drug or by the ISceI meganuclease. Timecourse analysis after cell exposure to ionizing radiation indicates that the decrease in chromatin mobility is transient and precedes subsequent increased mobility. Future applications of the method in the DNA repair field and beyond are discussed.

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Section: Resultssupporting

confidence: 71%

Section: Resultsmentioning

confidence: 99%

Section: Tools and Techniquesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nanoscale histone localization in live cells reveals reduced chromatin mobility in response to DNA damage

Liu

Vidi

Lelièvre

et al. 2014

Journal of Cell Science

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“…In most instances, the recruitment of chromatin remodelling factors is ATM dependent and is thus encompassed within the DDR signalling response. This subject has also been reviewed previously and will not be discussed in further detail here [74][75][76][77].…”

Section: Role Of Additional Chromatin Remodelling Factors In Dsb Repairmentioning

confidence: 99%

How cancer cells hijack DNA double-strand break repair pathways to gain genomic instability

Jeggo

Löbrich

2015

Biochemical Journal

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DNA DSBs (double-strand breaks) are a significant threat to the viability of a normal cell, since they can result in loss of genetic material if mitosis or replication is attempted in their presence. Consequently, evolutionary pressure has resulted in multiple pathways and responses to enable DSBs to be repaired efficiently and faithfully. Cancer cells, which are under pressure to gain genomic instability, have a striking ability to avoid the elegant mechanisms by which normal cells maintain genomic stability. Current models suggest that, in normal cells, DSB repair occurs in a hierarchical manner that promotes rapid and efficient rejoining first, with the utilization of additional steps or pathways of diminished accuracy if rejoining is unsuccessful or delayed. In the present review, we evaluate the fidelity of DSB repair pathways and discuss how cancer cells promote the utilization of less accurate processes. Homologous recombination serves to promote accuracy and stability during replication, providing a battlefield for cancer to gain instability. Non-homologous end-joining, a major DSB repair pathway in mammalian cells, usually operates with high fidelity and only switches to less faithful modes if timely repair fails. The transition step is finely tuned and provides another point of attack during tumour progression. In addition to DSB repair, a DSB signalling response activates processes such as cell cycle checkpoint arrest, which enhance the possibility of accurate DSB repair. We consider the ways by which cancers modify and hijack these processes to gain genomic instability.

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Nuclear Actin

Green

Kimble

Talbot

et al. 2021

Encyclopedia of Life Sciences

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While actin is a highly evolutionarily conserved protein that has been extensively studied for its role in the cytoskeleton, it also localises and functions within the nucleus. Tight regulation of both the level and form (monomeric vs filamentous) of nuclear actin is essential for many nuclear processes. Nuclear actin regulates transcription at multiple steps, including initiation, elongation and messenger ribonucleic acid (mRNA) processing. It also regulates chromatin organisation by controlling chromatin modifiers and mediating chromatin movement during transcription, deoxyribonucleic acid (DNA) repair and DNA replication. Finally, nuclear actin is a critical component of the nucleoskeleton, where it regulates nuclear structure and organisation, cellular response to mechanical signalling and nucleolar structure and function. These functions of nuclear actin are critical for maintaining cellular homeostasis, responding to cellular stress and mediating cell fate decisions. Key Concepts Different forms of nuclear actin regulate distinct aspects of transcription: G‐actin promotes the initiation of transcription and mediates the escape from pausing, whereas dynamic actin polymerisation is required for transcriptional elongation. Nuclear G‐actin acts as a scaffold to regulate the entire RNA biogenesis pathway from initiating transcription to translation. Both cytoplasmic and nuclear actin dynamics regulate SRF/MAL‐dependent transcription. Nuclear G‐actin directly interacts with histone modifiers and chromatin remodelling complexes to regulate chromatin accessibility for transcription, DNA repair and replication. Nuclear actin plays critical roles in the repair of DNA double‐strand breaks both by regulating chromatin remodelling complex activity and by F‐actin‐dependent chromatin movement or stabilisation of repair machinery. Nuclear F‐actin is also required for moving chromatin to and maintaining transcription factors and mediating DNA replication and chromosome segregation. Mechanotransduction impacts the nucleoskeleton to regulate the level and form of nuclear actin to mediate changes in transcription and chromatin organisation that drive the cell‐specific response to force. Actin localises and functions within the nucleolus and may mediate the nucleolar stress response. Tight regulation of nuclear actin level and/or polymerisation plays critical roles in cell fate transitions.

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Chromatin Movement in the Maintenance of Genome Stability

Cited by 205 publications

References 84 publications

Nanoscale histone localization in live cells reveals reduced chromatin mobility in response to DNA damage

Nanoscale histone localization in live cells reveals reduced chromatin mobility in response to DNA damage

How cancer cells hijack DNA double-strand break repair pathways to gain genomic instability

Nuclear Actin

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