Single-nucleosome imaging reveals principles of transient multiscale chromatin unfolding triggered by histone ADP-ribosylation at DNA lesions DOI Open Access
Fabiola García Fernández, Catherine Chapuis,

Junwoo Park

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 30, 2024

ABSTRACT Timely access to DNA lesions is crucial for genome integrity. This process requires profound remodeling of densely packed chromatin establish a repair-competent architecture. However, limited resolution has made it impossible fully understand these events. Here, combining microirradiation with live-cell multiscale imaging, we report that damage-induced changes in packing rely on the conformational behaviour fiber. Immediately after damage, transient increase nucleosome mobility switches from densely-packed state looser conformation, making accessible repair. While histone poly-ADP-ribosylation required trigger this switch, mono-ADP-ribosylation sufficient maintain open-chromatin state. The removal marks by ARH3 hydrolase then leads recondensation. Together, our study dynamics establishes global model: distinct waves ADP-ribosylation control mobility, triggering breathing chromatin, initiating damage response.

Язык: Английский

Mechanism for local attenuation of DNA replication at double-strand breaks DOI
Robin Sebastian, Eric G. Sun, Michael Fedkenheuer

и другие.

Nature, Год журнала: 2025, Номер unknown

Опубликована: Фев. 19, 2025

Язык: Английский

Процитировано

1
Perspectives and mechanisms for targeting mitotic catastrophe in cancer treatment DOI
Zhaoshi Bai, Yiran Zhou,

Yaling Peng

и другие.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2023, Номер 1878(5), С. 188965 - 188965

Опубликована: Авг. 23, 2023

Язык: Английский

Процитировано

19
The missing hallmark of health: psychosocial adaptation DOI
Carlos López‐Otín, Guido Kroemer

Cell Stress, Год журнала: 2024, Номер 8, С. 21 - 50

Опубликована: Янв. 1, 2024

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

Язык: Английский

Процитировано

7
SUMO and the DNA damage response DOI Creative Commons

Jai S. Bhachoo,

Alexander J. Garvin

Biochemical Society Transactions, Год журнала: 2024, Номер 52(2), С. 773 - 792

Опубликована: Апрель 17, 2024

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

Язык: Английский

Процитировано

6
Nucleotide excision repair of aflatoxin-induced DNA damage within the 3D human genome organization DOI Creative Commons
Yiran Wu, Muhammad Muzammal Adeel,

Dian Xia

и другие.

Nucleic Acids Research, Год журнала: 2024, Номер unknown

Опубликована: Авг. 21, 2024

Abstract Aflatoxin B1 (AFB1), a potent mycotoxin, is one of the environmental risk factors that cause liver cancer. In liver, bioactivated AFB1 intercalates into DNA double helix to form bulky adduct which will lead mutation if left unrepaired. Here, we adapted tXR-seq method measure nucleotide excision repair AFB1-induced adducts at single-nucleotide resolution on genome-wide scale, and compared it with data obtained from conventional UV-damage XR-seq. Our results showed transcription-coupled plays major role in damage removal process. We further analyzed distribution sites for within 3D human genome organization. analysis revealed heterogeneous AFB1–dG across four different organization levels, including chromosome territories, A/B compartments, TADs, chromatin loops. found chromosomes positioned closer nuclear center regions A compartments have higher levels repair. Notably, observed high activity around both TAD boundaries loop anchors. These findings provide insights complex interplay between repair, transcription, organization, shedding light mechanisms underlying mutagenesis.

Язык: Английский

Процитировано

5
Epigenetic state and gene expression remain stable after CRISPR/Cas‐mediated chromosomal inversions DOI Creative Commons
Solmaz Khosravi,

Rebecca Hinrichs,

Michelle Rönspies

и другие.

New Phytologist, Год журнала: 2025, Номер unknown

Опубликована: Янв. 29, 2025

Summary The epigenetic state of chromatin, gene activity and chromosomal positions are interrelated in plants. In Arabidopsis thaliana , chromosome arms DNA‐hypomethylated enriched with the euchromatin‐specific histone mark H3K4me3, while pericentromeric regions DNA‐hypermethylated heterochromatin‐specific H3K9me2. We aimed to investigate how location affects stability expression by engineering. Two inversions different sizes were induced using CRISPR/Cas9 move heterochromatic, pericentric sequences into euchromatic regions. status these lines was investigated whole‐genome bisulfite sequencing chromatin immunoprecipitation. Gene changes following induction studied via transcriptome analysis. Both had a minimal impact on global distribution marks DNA methylation patterns, although minor observed across genome. Notably, inverted their borders retained original profiles. analysis showed that only 0.5–1% genes differentially expressed genome‐wide inversions. CRISPR/Cas‐induced minimally affect landscape expression, preserving profiles subsequent generations.

Язык: Английский

Процитировано

0
A predictive chromatin architecture nexus regulates transcription and DNA damage repair DOI Creative Commons
Audesh Bhat,

Sonali Bhan,

Aindrila Kabiraj

и другие.

Journal of Biological Chemistry, Год журнала: 2025, Номер unknown, С. 108300 - 108300

Опубликована: Фев. 1, 2025

Genomes are blueprints of life essential for an organism's survival, propagation, and evolutionary adaptation. Eukaryotic genomes comprises DNA, core histones several other nonhistone proteins packaged into chromatin in the tiny nucleus. Chromatin structural organization restricts transcription protein DNA access, permitting binding only after specific remodelling events. The fundamental processes living cells, including transcription, replication, repair, recombination, thus regulated by structure through ATP-dependent remodelling, histone variant incorporation, various covalent modifications phosphorylation, acetylation, ubiquitination. These modifications, particularly involving H2AX, furthermore play crucial roles damage responses enabling repair access to damage. also stabilizes genome regulating mechanisms while suppressing from endogenous exogenous sources. Environmental factors such as ionizing radiations induce damage, if is compromised, can lead chromosomal abnormalities gene amplifications observed tumor types. Consequently architecture controls blueprint fidelity activity: it orchestrates correct expression, genomic integrity, recombination. This review considers connecting functional outcomes impacting integrity emerging grand challenge predictive molecular cell biology.

Язык: Английский

Процитировано

0
Neuronal somatic mutations are increased in multiple sclerosis lesions DOI
Allan Motyer,

Stacey Jackson,

Bicheng Yang

и другие.

Nature Neuroscience, Год журнала: 2025, Номер unknown

Опубликована: Март 4, 2025

Язык: Английский

Процитировано

0
N4-acetylcytidine and other RNA modifications in epitranscriptome: insight into DNA repair and cancer development DOI Creative Commons
Eva Bártová, Lenka Stixová,

Alena Svobodová Kovaříková

и другие.

Epigenomics, Год журнала: 2025, Номер unknown, С. 1 - 12

Опубликована: Март 5, 2025

N4-acetylcytidine (ac4C) is a post-transcriptional RNA modification that plays crucial role in the epitranscriptome, influencing gene expression and cellular function. This occurs at cytosine base, where an acetyl group installed to nitrogen 4th position (N4). co-transcription affects stability, structure, translation efficiency. Recent studies have uncovered potential link between modifications DNA repair mechanisms, suggesting ac4C-modified or methylated RNAs may interact with factors involved pathways; thus, response damage. Dysregulation of modified RNAs, including ac4C RNA, has been implicated cancer development, aberrant levels these contribute oncogenic transformation by altering genome stability key genes regulating cell proliferation, cycle progression, apoptosis. Understanding dynamics offers promising insights into epitranscriptome processes treatment.

Язык: Английский

Процитировано

0
Checkpoint kinases regulate the circadian clock after DNA damage by influencing chromatin dynamics DOI Creative Commons

Yulin Yang,

Zeyu Duan, Xiaolan Liu

и другие.

Nucleic Acids Research, Год журнала: 2025, Номер 53(5)

Опубликована: Фев. 27, 2025

The interplay between circadian clocks, the cell cycle, and DNA repair has been extensively documented, yet epigenetic control of clocks by damage responses remains relatively unexplored. Here, we showed that checkpoint kinases CHK1/2 regulate chromatin structure during in Neurospora crassa to maintain robust rhythms. Under stress, deletion chk1/2 disrupted rhythmic transcription clock gene frq suppressing binding activator White Collar complex (WCC) at promoter, as remained condensed. Mechanistically, interacted with WC-2 were recruited WCC bind promoter phosphorylate H3T11, promoting H3 acetylation, especially H3K56 counteract histone variant H2A.Z deposition, thereby establishing a suitable state rhythms despite damage. Additionally, genome-wide correlation was discovered H3T11 phosphorylation showing specific function is dependent on CHK1/2. Furthermore, transcriptome analysis revealed are responsible for metabolic genes These findings highlight essential role maintaining under stress.

Язык: Английский

Процитировано

0