The role of Smarcad1 in retroviral repression in mouse embryonic stem cells.

Background: Moloney murine leukemia virus (MLV) replication is suppressed in mouse embryonic stem cells (ESCs) by the Trim28-SETDB1 complex. The chromatin remodeler Smarcad1 interacts with Trim28 and was suggested to allow the deposition of the histone variant H3.3.

Short heat shock has a long-term effect on mesenchymal stem cells' transcriptome.

The adverse effects of heat stress (HS) on physiological systems are well documented, yet the underlying molecular mechanisms behind it remain poorly understood. To address this knowledge gap, we conducted a comprehensive investigation into the impact of HS on mesenchymal stem cells (MSCs), focusing on their morphology, phenotype, proliferative capacity, and fate determination. Our in-depth analysis of the MSCs' transcriptome revealed a significant influence of HS on the transcriptional landscape.

Differential effect of histone H3.3 depletion on retroviral repression in embryonic stem cells.

Background: Integration of retroviruses into the host genome can impair the genomic and epigenomic integrity of the cell. As a defense mechanism, epigenetic modifications on the proviral DNA repress retroviral sequences in mouse embryonic stem cells (ESC). Here, we focus on the histone 3 variant H3.

Antioxidants Attenuate Heat Shock Induced Premature Senescence of Bovine Mesenchymal Stem Cells.

Mesenchymal stem cells (MSC) have many roles that are important for the body's proper functioning. When the MSC pool is damaged, it is often correlated with impaired development or health of the organism. MSC are known for their anti-inflammatory, immunomodulatory and trophic characteristics that play an important role in the physiological homeostasis of many tissues.

Heat Shock Alters Mesenchymal Stem Cell Identity and Induces Premature Senescence.

Heat stress can have a serious impact on the health of both humans and animals. A major question is how heat stress affects normal development and differentiation at both the cellular and the organism levels. Here we use an experimental system to address how heat shock treatment influences the properties of bovine mesenchymal stem cells (MSCs)-multipotent progenitor cells-which are found in most tissues.

Trim24 and Trim33 Play a Role in Epigenetic Silencing of Retroviruses in Embryonic Stem Cells.

Embryonic stem cells (ESC) have the ability to epigenetically silence endogenous and exogenous retroviral sequences. Trim28 plays an important role in establishing this silencing, but less is known about the role other Trim proteins play. The Tif1 family is a sub-group of the Trim family, which possess histone binding ability in addition to the distinctive RING domain.

Structured Benefit-Risk Assessment Across the Product Lifecycle: Practical Considerations.

Background: Assessing the benefit-risk profile of a medicinal product is a complex but fundamental activity that sponsors and regulators must perform throughout the product's lifecycle. In order to improve the transparency and consistency of the decision-making process, regulators and sponsors alike are increasingly applying a structured approach to benefit-risk assessment. However, to our knowledge, there has been little practical guidance in the published literature regarding how to embed such a process organizationally.

The DNA2 nuclease/helicase is an estrogen-dependent gene mutated in breast and ovarian cancers.

Genomic instability, a hallmark of cancer, is commonly caused by failures in the DNA damage response. Here we conducted a bioinformatical screen to reveal DNA damage response genes that are upregulated by estrogen and highly mutated in breast and ovarian cancers. This screen identified 53 estrogen-dependent cancer genes, some of which are novel.

Recruitment of proteins to DNA double-strand breaks: MDC1 directly recruits RAP80.

DNA double-strand breaks (DSBs) are the most severe type of DNA damage. Occurrence of DSBs in the cell activates the DNA damage response (DDR), which involves signaling cascades that sense and respond to the damage. Promptly after DSB induction, DDR proteins accumulate surrounding both DNA ends and form microscopically-visible foci.

MDC1 is ubiquitylated on its tandem BRCT domain and directly binds RAP80 in a UBC13-dependent manner.

The cellular response to DNA damage is essential for maintenance of genomic stability. MDC1 is a key member of the DNA damage response. It is an adaptor protein that binds and recruits proteins to sites of DNA damage, a crucial step for a proper response.

The DNA damage response mediator MDC1 directly interacts with the anaphase-promoting complex/cyclosome.

MDC1 (NFBD1), a mediator of the cellular response to DNA damage, plays an important role in checkpoint activation and DNA repair. Here we identified a cross-talk between the DNA damage response and cell cycle regulation. We discovered that MDC1 binds the anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase that controls the cell cycle.