MYC, mitochondrial metabolism and O-GlcNAcylation converge to modulate the activity and subcellular localization of DNA and RNA demethylases

Nucleotides are essential to cell growth and survival, providing cells with building blocks for DNA and RNA, energy carriers, and cofactors. Mitochondria have a critical role in the production of intracellular ATP and participate in the generation of intermediates necessary for biosynthesis of macromolecules such as purines and pyrimidines. In this review, we highlight the role of purine and mitochondrial metabolism in cancer and how their intersection influences cancer progression, especially in ovarian cancer. Additionally, we address the importance of metabolic rewiring in cancer and how the evolving landscape of purine synthesis and mitochondria inhibitors can be potentially exploited for cancer treatment.

Download Full-text

High-resolution nucleic acid sequence mapping via in situ hybridization at the Electron Microscope level

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100140130 ◽

1995 ◽

Vol 53 ◽

pp. 752-753

Author(s):

B.A. Hamkalo ◽

S. Narayanswami ◽

A.P. Kausch

Keyword(s):

Nucleic Acid ◽

Interphase Nucleus ◽

Genome Mapping ◽

Precise Location ◽

Electron Microscope Level ◽

Rna Sequences ◽

Fundamental Interest ◽

Whole Cells ◽

Dna And Rna

The availability of nonradioactive methods to label nucleic acids an the resultant rapid and greater sensitivity of detection has catapulted the technique of in situ hybridization to become the method of choice to locate of specific DNA and RNA sequences on chromosomes and in whole cells in cytological preparations in many areas of biology. It is being applied to problems of fundamental interest to basic cell and molecular biologists such as the organization of the interphase nucleus in the context of putative functional domains; it is making major contributions to genome mapping efforts; and it is being applied to the analysis of clinical specimens. Although fluorescence detection of nucleic acid hybrids is routinely used, certain questions require greater resolution. For example, very closely linked sequences may not be separable using fluorescence; the precise location of sequences with respect to chromosome structures may be below the resolution of light microscopy(LM); and the relative positions of sequences on very small chromosomes may not be feasible.

Download Full-text

Scanning tunneling microscopy (STM) of DNA and RNA

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100152148 ◽

1989 ◽

Vol 47 ◽

pp. 34-35

Author(s):

Patricia G. Arscott ◽

Gil Lee ◽

Victor A. Bloomfield ◽

D. Fennell Evans

Keyword(s):

Molecular Structures ◽

Inorganic Materials ◽

Resolving Power ◽

Scanning Tunneling ◽

Tunneling Microscopy ◽

Form And Function ◽

Dna And Rna ◽

Calf Thymus ◽

And Function ◽

The Relationship

STM is one of the most promising techniques available for visualizing the fine details of biomolecular structure. It has been used to map the surface topography of inorganic materials in atomic dimensions, and thus has the resolving power not only to determine the conformation of small molecules but to distinguish site-specific features within a molecule. That level of detail is of critical importance in understanding the relationship between form and function in biological systems. The size, shape, and accessibility of molecular structures can be determined much more accurately by STM than by electron microscopy since no staining, shadowing or labeling with heavy metals is required, and there is no exposure to damaging radiation by electrons. Crystallography and most other physical techniques do not give information about individual molecules.We have obtained striking images of DNA and RNA, using calf thymus DNA and two synthetic polynucleotides, poly(dG-me5dC)·poly(dG-me5dC) and poly(rA)·poly(rU).

Download Full-text

Investigating the functional link between TMEM165 and SPCA1

Biochemical Journal ◽

10.1042/bcj20190488 ◽

2019 ◽

Vol 476 (21) ◽

pp. 3281-3293 ◽

Cited By ~ 2

Author(s):

Elodie Lebredonchel ◽

Marine Houdou ◽

Hans-Heinrich Hoffmann ◽

Kateryna Kondratska ◽

Marie-Ange Krzewinski ◽

...

Keyword(s):

Subcellular Localization ◽

Complete Loss ◽

Protein Family ◽

Uncharacterized Protein ◽

Functional Link ◽

P Type

TMEM165 was highlighted in 2012 as the first member of the Uncharacterized Protein Family 0016 (UPF0016) related to human glycosylation diseases. Defects in TMEM165 are associated with strong Golgi glycosylation abnormalities. Our previous work has shown that TMEM165 rapidly degrades with supraphysiological manganese supplementation. In this paper, we establish a functional link between TMEM165 and SPCA1, the Golgi Ca2+/Mn2+ P-type ATPase pump. A nearly complete loss of TMEM165 was observed in SPCA1-deficient Hap1 cells. We demonstrate that TMEM165 was constitutively degraded in lysosomes in the absence of SPCA1. Complementation studies showed that TMEM165 abundance was directly dependent on SPCA1's function and more specifically its capacity to pump Mn2+ from the cytosol into the Golgi lumen. Among SPCA1 mutants that differentially impair Mn2+ and Ca2+ transport, only the Q747A mutant that favors Mn2+ pumping rescues the abundance and Golgi subcellular localization of TMEM165. Interestingly, the overexpression of SERCA2b also rescues the expression of TMEM165. Finally, this paper highlights that TMEM165 expression is linked to the function of SPCA1.

Download Full-text