Tracing Extrachromosomal DNA Inheritance Patterns in Glioblastoma Using CRISPR

MedicalResearch.com Interview with:

Eunhee Yi, Ph.D.Postdoctoral AssociateThe Jackson Laboratory

Dr. Yi

Eunhee Yi, Ph.D.
Postdoctoral Associate
The Jackson Laboratory

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Recurrence after therapy for glioblastoma (GBM) is unavoidable. There are substantial differences among the cells of GBM tumors in the abundance and types of genetic materials. This heterogeneity is a major driver of therapy failure and disease progression. We previously reported that extrachromosomal DNA (ecDNA) elements, which reside outside the linear genome and represent a mechanism to amplify and activate oncogenes, is a potential cause of the increasing genetic diversity in GBM. Our current study is focused on the development of a novel cytogenetic tool to visualize ecDNA to visualize the behavior of these elements in live cells. We have leveraged the unique properties of ecDNA to develop a CRISPR-based “ecDNA tracing toolbox (EDTB)”.  Continue reading

Distinct Methylation May Explain Why Some People’s DNA Ages More Slowly

Dr-Bastiaan-Heijmans.jpg

MedicalResearch.com Interview with:
Dr. Bastiaan Heijmans
Leiden University Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Epigenetic change is a hallmark of ageing but its link to ageing mechanisms in humans remains poorly understood. While DNA methylation at many CpG sites closely tracks chronological age, DNA methylation changes relevant to biological age are expected to gradually dissociate from chronological age, mirroring the increased heterogeneity in health status at older ages.

In a large-scale analysis of the methylome of over 3000 individuals, we discovered and validated 6000 sites in the genome that became more variable in their DNA methylation level with age. These sites frequently co-localized with repressed regions that are characterized by polycomb repression. While sites accumulating variability with age were commonly associated with the expression of (neuro)developmental genes in cis, they were linked to transcriptional activity of genes in trans that have a key role in well-established ageing pathways such as intracellular metabolism, apoptosis, and DNA damage response.

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Expanded Genetic DNA More Susceptible To Ultraviolet Light Damage

MedicalResearch.com Interview with:

Carlos E. Crespo-Hernández PhD Associate Professor and Co-director of the Center for Chemical Dynamics Department of Chemistry Case Western Reserve University Cleveland, Ohio

Dr. Carlos E. Crespo-Hernández

Carlos E. Crespo-Hernández PhD
Associate Professor and Co-director of the Center for Chemical Dynamics
Department of Chemistry
Case Western Reserve University
Cleveland, Ohio

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Two new letters of DNA have recently been successfully incorporated and replicated by a modified strain of E. coli, thus generating the world’s first semi-synthetic organism with an expanded genetic alphabet. With the expansion of the genetic alphabet, the question arises as to whether the incorporation of unnatural DNA base pairs into cells can adversely affect the integrity of the genetic code and the viability of the cells upon exposure to sunlight or even conventional laboratory lighting. Natural DNA is susceptible to damage by ultraviolet light, but this damage is largely repaired by enzymatic repair mechanisms in living cells. Our recent study has found that the two new, unnatural DNA bases—d5SICS and dNaM—are able to efficiently absorb near-visible light, which is abundant in sunlight and standard fluorescent lighting. Not only that, but upon absorbing near-visible light these unnatural bases produce up to 100 times more reactive species than the most reactive natural DNA base. A line of skin cancer cells incorporating one of these unnatural DNA bases was used to investigate these effects on living cells. Following exposure to a low dose of near-visible light, we observed an increase in the generation of reactive oxygen species within cells containing the unnatural DNA base and a significant decrease in cell survival.

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