The DNA damage response in the chromatin context: A coordinated process

Dabin, Juliette; Mori, Margherita; Polo, Sophie E.

doi:10.1016/j.ceb.2023.102176

Cited by 14 publications

(5 citation statements)

References 61 publications

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“…Nuclear and mitochondrial DNA are constantly subjected to genotoxic stress by exogenous and endogenous challenges. This causes a wide spectrum of DNA lesions, which are repaired by a network of systems collectively known as the DNA damage response (DDR) [ 253 ]. The effectors of this response, such as TP53 and various immune cells, drive cellular senescence or apoptosis and contribute to maintain homeostasis.…”

Section: Hallmark 8: Repair and Regenerationmentioning

confidence: 99%

The missing hallmark of health: psychosocial adaptation

López-Otín,

Kroemer

2024

CST

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The eight biological hallmarks of health that we initially postulated (Cell. 2021 Jan 7;184(1):33-63) include features of spatial compartmentalization (integrity of barriers, containment of local perturbations), maintenance of homeostasis over time (recycling & turnover, integration of circuitries, rhythmic oscillations) and an array of adequate responses to stress (homeostatic resilience, hormetic regulation, repair & regeneration). These hallmarks affect all eight somatic strata of the human body (molecules, organelles, cells, supracellular units, organs, organ systems, systemic circuitries and meta-organism). Here we postulate that mental and socioeconomic factors must be added to this 8×8 matrix as an additional hallmark of health (“psychosocial adaptation”) and as an additional stratum (“psychosocial interactions”), hence building a 9×9 matrix. Potentially, perturbation of each of the somatic hallmarks and strata affects psychosocial factors and vice versa. Finally, we discuss the (patho)physiological bases of these interactions and their implications for mental health improvement.

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Section: Hallmark 8: Repair and Regenerationmentioning

confidence: 99%

The missing hallmark of health: psychosocial adaptation

López-Otín,

Kroemer

2024

CST

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“…The chromatin landscape plays a significant role in DDR [ 155 , 156 ]. The SUMO proteome is enriched in chromatin remodellers which are dynamically modified during DNA damage signalling [ 11 , 146 , 157 ].…”

Section: Sumoylation and Chromatinmentioning

confidence: 99%

SUMO and the DNA damage response

Bhachoo,

Garvin

2024

Biochemical Society Transactions

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The preservation of genome integrity requires specialised DNA damage repair (DDR) signalling pathways to respond to each type of DNA damage. A key feature of DDR is the integration of numerous post-translational modification signals with DNA repair factors. These modifications influence DDR factor recruitment to damaged DNA, activity, protein-protein interactions, and ultimately eviction to enable access for subsequent repair factors or termination of DDR signalling. SUMO1-3 (small ubiquitin-like modifier 1-3) conjugation has gained much recent attention. The SUMO-modified proteome is enriched with DNA repair factors. Here we provide a snapshot of our current understanding of how SUMO signalling impacts the major DNA repair pathways in mammalian cells. We highlight repeating themes of SUMO signalling used throughout DNA repair pathways including the assembly of protein complexes, competition with ubiquitin to promote DDR factor stability and ubiquitin-dependent degradation or extraction of SUMOylated DDR factors. As SUMO ‘addiction’ in cancer cells is protective to genomic integrity, targeting components of the SUMO machinery to potentiate DNA damaging therapy or exacerbate existing DNA repair defects is a promising area of study.

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“…For efficient DNA repair, the accessibility of the damaged region also plays a major role. Moreover, the detailed structure of the DNA at the time of repair is important to support proper repair and decrease the probability of mis- or un-joined DNA ends [ 37 ]. The accumulation of DNA repair proteins at the damaged DNA locus is highly dependent on the accessibility of the damage.…”

Section: Introductionmentioning

confidence: 99%

Chromatin Organization after High-LET Irradiation Revealed by Super-Resolution STED Microscopy

Schwarz,

Matejka,

Rudigkeit

et al. 2024

IJMS

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Ion-radiation-induced DNA double-strand breaks can lead to severe cellular damage ranging from mutations up to direct cell death. The interplay between the chromatin surrounding the damage and the proteins responsible for damage recognition and repair determines the efficiency and outcome of DNA repair. The chromatin is organized in three major functional compartments throughout the interphase: the chromatin territories, the interchromatin compartment, and the perichromatin lying in between. In this study, we perform correlation analysis using super-resolution STED images of chromatin; splicing factor SC35, as an interchromatin marker; and the DNA repair factors 53BP1, Rad51, and γH2AX in carbon-ion-irradiated human HeLa cells. Chromatin and interchromatin overlap only in protruding chromatin branches, which is the same for the correlation between chromatin and 53BP1. In contrast, between interchromatin and 53BP1, a gap of (270 ± 40) nm is visible. Rad51 shows overlap with decondensed euchromatic regions located at the borders of condensed heterochromatin with further correlation with γH2AX. We conclude that the DNA damage is repaired in decondensed DNA loops in the perichromatin, located in the periphery of the DNA-dense chromatin compartments containing the heterochromatin. Proteins like γH2AX and 53BP1 serve as supporters of the chromatin structure.

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The DNA damage response in the chromatin context: A coordinated process

Cited by 14 publications

References 61 publications

The missing hallmark of health: psychosocial adaptation

The missing hallmark of health: psychosocial adaptation

SUMO and the DNA damage response

Chromatin Organization after High-LET Irradiation Revealed by Super-Resolution STED Microscopy

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