BRUCE preserves genomic stability in the male germline of mice

Che, Lixiao; Alavattam, Kris G.; Stambrook, Peter J.; Namekawa, Satoshi H.; Du, Can

doi:10.1038/s41418-020-0513-4

Cited by 6 publications

(5 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To confirm the reversal of MSCI, we then performed gene-specific RNA Fluorescence in situ hybridization (FISH) to detect nascent transcripts of two X-linked genes ( Utx/Kdm6a and Lamp2 at 18 Mb and 37 Mb on the X chromosome, respectively (Fig. 1g, h ) using our previously validated RNA FISH probes 37 , 38 . After 24 h of treatment with AZ20, Utx and Lamp2 were actively transcribed in 87% and 98% of pachytene spermatocytes, while these genes were inactive in controls (Fig.…”

Section: Resultsmentioning

confidence: 99%

Active DNA damage response signaling initiates and maintains meiotic sex chromosome inactivation

et al. 2022

Self Cite

View full text Add to dashboard Cite

Meiotic sex chromosome inactivation (MSCI) is an essential process in the male germline. While genetic experiments have established that the DNA damage response (DDR) pathway directs MSCI, due to limitations to the experimental systems available, mechanisms underlying MSCI remain largely unknown. Here we establish a system to study MSCI ex vivo, based on a short-term culture method, and demonstrate that active DDR signaling is required both to initiate and maintain MSCI via a dynamic and reversible process. DDR-directed MSCI follows two layers of modifications: active DDR-dependent reversible processes and irreversible histone post-translational modifications. Further, the DDR initiates MSCI independent of the downstream repressive histone mark H3K9 trimethylation (H3K9me3), thereby demonstrating that active DDR signaling is the primary mechanism of silencing in MSCI. By unveiling the dynamic nature of MSCI, and its governance by active DDR signals, our study highlights the sex chromosomes as an active signaling hub in meiosis.

show abstract

Section: Resultsmentioning

confidence: 99%

Active DNA damage response signaling initiates and maintains meiotic sex chromosome inactivation

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…After incubation with the secondary antibodies, the plate was washed thoroughly, and a solution of 3,3′,5,5′-tetramethylbenzidine substrate was added. A sulfuric acid solution was added to stop the reaction, and the color was analyzed using spectrophotometry at a wavelength of 450 nm [28]. The concentrations of SOD, GPX, GSH, and MDA in the culture media were then calculated according to the standard curve [29].…”

Section: Cardiac Endothelial Cells (Cecs)mentioning

confidence: 99%

Coronary Endothelium No‐Reflow Injury Is Associated with ROS‐Modified Mitochondrial Fission through the JNK‐Drp1 Signaling Pathway

Chen

Liu

Zhou

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Coronary artery no-reflow is a complex problem in the area of reperfusion therapy, and the molecular mechanisms underlying coronary artery no-reflow injury have not been fully elucidated. In the present study, we explored whether oxidative stress caused damage to coronary endothelial cells by inducing mitochondrial fission and activating the JNK pathway. The hypoxia/reoxygenation (H/R) model was induced in vitro to mimic coronary endothelial no-reflow injury, and mitochondrial fission, mitochondrial function, and endothelial cell viability were analyzed using western blotting, quantitative polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence. Our data indicated that reactive oxygen species (ROS) were significantly induced upon H/R injury, and this was followed by decreased endothelial cell viability. Mitochondrial fission was induced and mitochondrial bioenergetics were impaired in cardiac endothelial cells after H/R injury. Neutralization of ROS reduced mitochondrial fission and protected mitochondrial function against H/R injury. Our results also demonstrated that ROS stimulated mitochondrial fission via JNK-mediated Drp1 phosphorylation. These findings indicate that the ROS-JNK-Drp1 signaling pathway may be one of the molecular mechanisms underlying endothelial cell damage during H/R injury. Novel treatments for coronary no-reflow injury may involve targeting mitochondrial fission and the JNK-Drp1 signaling pathway.

show abstract

“…Moreover, transcripts required for protection from oxidative stress ( Fermt1, Smg1 ) 25 , 26 and recovery from DNA damage ( Tlk2, Rad54l ) 27 , 28 showed a significant ( P < 0.05) overexpression. In contrast, amongst the most significantly downregulated transcripts, cingulin ( Cgn ) a tight junction protein known to cause activation of cellular senescence pathways following its functional ablation 29 , Birc6/Bruce , an inhibitor of apoptosis 30 that regulates DNA double-strand break response 31 and is required for genome stability 32 as well as the N-Ras proto-oncogene, which is required to modulate the DNA damage response 33 were all downregulated >20 fold. In addition, Rev1 a translesion synthesis protein that regulates radiation resistance 34 and Dnmt3l were downregulated >5 fold.…”

Section: Resultsmentioning

confidence: 99%

“…Transcripts for Birc6/Bruce were downregulated >20 fold. Birc6 is required for homologous recombination in somatic cells and prevents non-homologous chromosome interactions during spermatogenesis 32 . Collectively, our results indicate that γ-irradiation activates signaling pathways associated with the onset of cellular senescence as well as repair from DNA damage and suggest a mechanistic link between the DNA damage response and regulation of large-scale heterochromatin structure in the oocyte genome.…”

Section: Discussionmentioning

confidence: 99%

Acute irradiation induces a senescence-like chromatin structure in mammalian oocytes

Baumann,

Zhang,

Kandasamy

et al. 2023

Commun Biol

View full text Add to dashboard Cite

The mechanisms leading to changes in mesoscale chromatin organization during cellular aging are unknown. Here, we used transcriptional activator-like effectors, RNA-seq and superresolution analysis to determine the effects of genotoxic stress on oocyte chromatin structure. Major satellites are organized into tightly packed globular structures that coalesce into chromocenters and dynamically associate with the nucleolus. Acute irradiation significantly enhanced chromocenter mobility in transcriptionally inactive oocytes. In transcriptionally active oocytes, irradiation induced a striking unfolding of satellite chromatin fibers and enhanced the expression of transcripts required for protection from oxidative stress (Fermt1, Smg1), recovery from DNA damage (Tlk2, Rad54l) and regulation of heterochromatin assembly (Zfp296, Ski-oncogene). Non-irradiated, senescent oocytes exhibit not only high chromocenter mobility and satellite distension but also a high frequency of extra chromosomal satellite DNA. Notably, analysis of biological aging using an oocyte-specific RNA clock revealed cellular communication, posttranslational protein modifications, chromatin and histone dynamics as the top cellular processes that are dysregulated in both senescent and irradiated oocytes. Our results indicate that unfolding of heterochromatin fibers following acute genotoxic stress or cellular aging induced the formation of distended satellites and that abnormal chromatin structure together with increased chromocenter mobility leads to chromosome instability in senescent oocytes.

show abstract

BRUCE preserves genomic stability in the male germline of mice

Cited by 6 publications

References 66 publications

Active DNA damage response signaling initiates and maintains meiotic sex chromosome inactivation

Active DNA damage response signaling initiates and maintains meiotic sex chromosome inactivation

Coronary Endothelium No‐Reflow Injury Is Associated with ROS‐Modified Mitochondrial Fission through the JNK‐Drp1 Signaling Pathway

Acute irradiation induces a senescence-like chromatin structure in mammalian oocytes

Contact Info

Product

Resources

About