Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.3 (topoisomerase)
 9,911 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apoptosis is a natural form of cell death involved in many physiological changes in the cell. Defects in the process of apoptosis can lead to serious diseases. During some apoptotic pathways, proteins apoptosis-inducing factor (AIF) and endonuclease G (EndoG) are released from the mitochondria and they translocate into the cell nuclei, where they probably participate in chromatin degradation together with other nuclear proteins. Exact mechanism of EndoG activity in cell nucleus is still unknown. Some interacting partners like flap endonuclease 1, DNase I, and exonuclease III were already suggested, but also other interacting partners were proposed. We conducted a living-cell confocal fluorescence microscopy followed by an image analysis of fluorescence resonance energy transfer to analyze the possibility of protein interactions of EndoG with histone H2B and human DNA topoisomerase II alpha (TOPO2a). Our results show that EndoG interacts with both these proteins during apoptotic cell death. Therefore, we can conclude that EndoG and TOPO2a may actively participate in apoptotic chromatin degradation. The possible existence of a degradation complex consisting of EndoG and TOPO2a and possibly other proteins like AIF and cyclophilin A have yet to be investigated.
 ...
PMID:Endonuclease G interacts with histone H2B and DNA topoisomerase II alpha during apoptosis. 2216 Aug 58

Male germ cells have a unique morphology and function to facilitate fertilization. Sperm deoxyribonucleic acid (DNA) is highly condensed to protect the paternal genome during transfer from male to oocyte. Sperm cells undergo extensive epigenetic modifications during differentiation to become a mature spermatozoon. Epigenetic modifications, including DNA methylation, histone modifications, and chromatin remodeling are substantial regulators of spermatogenesis. DNA hypermethylation is associated with gene silencing. Meanwhile, hypomethylation is associated with gene expression. In sperm cells, promoters of developmental genes are highly hypomethylated. Proper DNA methylation is essential for embryo development. Histone modifications are chemical modifications that change the DNA-binding capacity of histones and the accessibility of regulatory factors to the DNA, thereby altering gene expression. Phosphorylation, methylation, acetylation, and ubiquitination are primary modifications of lysine and serine residues on histone tails. In addition to somatic histones, testis-specific histone variants are expressed, including histone H2B in mature sperm. The replacement of histones with protamines is a crucial step in spermatogenesis. Histone hyper-acetylation induces a loose chromatin structure and facilitates topoisomerase-induced DNA strand breaks. As a result, histones are replaced with transition proteins. Next, the transition proteins are replaced with protamines that induce compaction of sperm DNA. This review provides an overview of epigenetic changes during spermatogenesis.
...
PMID:The role of epigenetics in spermatogenesis. 2632 5