Cellular senescence is a mechanism that induces an irreversible growth arrest in all somatic cells. Senescent cells are metabolically active but lack the capacity to replicate. Evolutionary theories suggest that cellular senescence is related to the organismal decline occurring in aging organisms. Also, such theories describe senescence as an antagonistically pleiotropic process that can have beneficial or detrimental effect on the organism. Cellular senescence is believed to be involved in the cellular changes observed as aging progresses. Accumulation of senescent cells appears to occur widely as the organism ages. Furthermore, senescence is a key element of the tumor suppressor pathways. Therefore, it is part of the natural barrier against the uncontrolled proliferation observed in cellular development of malignancies in multicellular organisms. Activation of the senescence process guarantees a limited number of cellular replications. The genetic network led by p53 is responsible for activation of senescence in response to DNA damage and genomic instability that could lead to cancer. A better comprehension of the genetic networks that control the cell cycle and induce senescence is important to analyze the association of senescence to longevity and diseases related to aging. For these reasons, experimental research both in vitro and in vivo aims to develop anticancer therapies based on senescence activation. The last decade of research on role and function of senescence in aging and cancer are discussed in this paper.
Aging ; Cell Aging ; Cell Cycle ; Comprehension ; DNA Damage ; Genomic Instability ; Longevity ; Telomere

The Ribonucleotide reductases (RNR) are essential enzymes that catalyze the conversion of nucleotides to deoxynucleotides in DNA replication and repair in all living organisms. The RNRs operate by a free radical mechanism but differ in the composition of subunit, cofactor required and regulation by allostery. Based on these differences the RNRs are classified into three classes-class I, class II and class III which depend on oxygen, adenosylcobalamin and S-adenosylmethionine with an iron sulfur cluster respectively for radical generation. In this article thirty seven sequences belonging to each of the three classes of RNR were analyzed by using various tools of bioinformatics. Phylogenetic analysis, dot-plot comparisons and motif analysis was done to identify a number of differences in the three classes of RNRs. In this research article, we have attempted to decipher evolutionary relationship between the three classes of RNR by using bioinformatics approach.
Cobamides ; Computational Biology ; DNA Replication ; Iron ; Nucleotides ; Oxygen ; Ribonucleotide Reductases ; S-Adenosylmethionine ; Sulfur

Heat shock proteins are a class of molecular chaperones that can be found in nearly all organisms from Bacteria, Archaea and Eukarya domains. Heat shock proteins experience increased transcription during periods of heat induced osmotic stress and are involved in protein disaggregation and refolding as part of a cell's danger signaling cascade. Heat shock protein, Hsp20 is a small molecular chaperone that is approximately 20kDa in weight and is hypothesized to prevent aggregation and denaturation. Hsp20 can be found in several strains of Proteobacteria, which comprises the largest phyla of the Bacteria domain and also contains several medically significant bacterial strains. Genomic analyses were performed to determine a common evolutionary pattern among Hsp20 sequences in Proteobacteria. It was found that Hsp20 shared a common ancestor within and among the five subclasses of Proteobacteria.This is readily apparent from the amount of sequence similarities within and between Hsp20 protein sequences as well as phylogenetic analysis of sequences from proteobacterial and non-proteobacterial species.
Actinobacteria ; Archaea ; Bacteria ; Computational Biology ; Eukaryota ; Heat-Shock Proteins ; Hot Temperature ; Molecular Chaperones ; Proteins ; Proteobacteria ; Shock

Protein kinase C (PKC) is a family of kinases involved in the transduction of cellular signals that promote lipid hydrolysis. PKC plays a pivotal role in mediating cellular responses to extracellular stimuli involved in proliferation, differentiation and apoptosis. Comparative analysis of the PKC-alpha, beta, epsilon isozymes of 200 recently sequenced microbial genomes was carried out using variety of bioinformatics tools. Diversity and evolution of PKC was determined by sequence alignment. The ser/thr protein kinases of Streptomyces coelicolor A3 (2), is the only bacteria to show sequence alignment score greater than 30% with all the three PKC isotypes in the sequence alignment. S.coelicolor is the subject of our interest because it is notable for the production of pharmaceutically useful compounds including anti-tumor agents, immunosupressants and over two-thirds of all natural antibiotics currently available. The comparative analysis of three human isotypes of PKC and Serine/threonine protein kinase of S.coelicolor was carried out and possible mechanism of action of PKC was derived. Our analysis indicates that Serine/ threonine protein kinase from S. coelicolor can be a good candidate for potent anti-tumor agent. The presence of three representative isotypes of the PKC super family in this organism helps us to understand the mechanism of PKC from evolutionary perspective.
Anti-Bacterial Agents ; Apoptosis ; Bacteria ; Computational Biology ; Genome ; Humans ; Hydrolysis ; Isoenzymes ; Negotiating ; Phosphotransferases ; Protein Kinase C ; Protein Kinases ; Sequence Alignment ; Sequence Analysis ; Streptomyces ; Streptomyces coelicolor ; Threonine

Protein kinase C (PKC) is a family of kinases involved in the transduction of cellular signals that promote lipid hydrolysis. PKC plays a pivotal role in mediating cellular responses to extracellular stimuli involved in proliferation, differentiation and apoptosis. Comparative analysis of the PKC-alpha, beta, epsilon isozymes of 200 recently sequenced microbial genomes was carried out using variety of bioinformatics tools. Diversity and evolution of PKC was determined by sequence alignment. The ser/thr protein kinases of Streptomyces coelicolor A3 (2), is the only bacteria to show sequence alignment score greater than 30% with all the three PKC isotypes in the sequence alignment. S.coelicolor is the subject of our interest because it is notable for the production of pharmaceutically useful compounds including anti-tumor agents, immunosupressants and over two-thirds of all natural antibiotics currently available. The comparative analysis of three human isotypes of PKC and Serine/threonine protein kinase of S.coelicolor was carried out and possible mechanism of action of PKC was derived. Our analysis indicates that Serine/ threonine protein kinase from S. coelicolor can be a good candidate for potent anti-tumor agent. The presence of three representative isotypes of the PKC super family in this organism helps us to understand the mechanism of PKC from evolutionary perspective.
Anti-Bacterial Agents ; Apoptosis ; Bacteria ; Computational Biology ; Genome ; Humans ; Hydrolysis ; Isoenzymes ; Negotiating ; Phosphotransferases ; Protein Kinase C ; Protein Kinases ; Sequence Alignment ; Sequence Analysis ; Streptomyces ; Streptomyces coelicolor ; Threonine

Monofunctional biosynthetic peptidoglycan transglycosylase (MBPT) catalyzes the formation of the glycan chain in bacterial cell walls from peptidoglycan subunits: N-acetylglucosamine (NAG) and acetylmuramic acid (NAM). Bifunctional glycosyltransferases such as the penicillin binding protein (PBP) have peptidoglycan glycosyltransferase (PGT) on their C terminal end which links together the peptidoglycan subunits while transpeptidase (TP) on the N terminal end cross-links the peptide moieties on the NAM monosaccharide of the peptide subunits to create the bacterial cell wall. The singular function of MBPT resembles the C terminal end of PBP as it too contains and utilizes a similar PGT domain. In this article we analyzed the infectious and non infectious protein sequences of MBPT from 31 different strains of bacteria using a variety of bioinformatic tools. Motif analysis, dot-plot comparison, and phylogenetic analysis identified a number of significant differences between infectious and non-infectious protein sequences. In this paper we have made an attempt to explain, analyze and discuss these differences from an evolutionary perspective. The results of our sequence analysis may open the door for utilizing MBPT as a new target to fight a variety of infectious bacteria.
Bacteria ; Cell Wall ; Glycosyltransferases ; Muramic Acids ; Penicillin-Binding Proteins ; Penicillins ; Peptidoglycan ; Peptidoglycan Glycosyltransferase ; Sequence Analysis