scholarly journals Transcriptional Regulation of the Human Genes that Encode DNA Repair- and Mitochondrial Function-Associated Proteins

10.5772/59588 ◽  
2015 ◽  
Author(s):  
Fumiaki Uchiumi ◽  
Steven Larsen ◽  
Sei-ichi Tanuma
Keyword(s):  
Dna Repair ◽  
Transcriptional Regulation ◽  
Mitochondrial Function ◽  
Human Genes ◽  
Associated Proteins

scholarly journals Multiple Promoters Contribute to Swarming and the Coordination of Transcription with Flagellar Assembly in Salmonella

2010 ◽  
Vol 192 (18) ◽  
pp. 4752-4762 ◽  
Author(s):  
Christopher E. Wozniak ◽  
Fabienne F. V. Chevance ◽  
Kelly T. Hughes
Keyword(s):  
Transcriptional Regulation ◽  
Stationary Phase ◽  
Basal Body ◽  
Environmental Conditions ◽  
Swarming Motility ◽  
Multiple Promoters ◽  
Associated Proteins ◽  
Flagellar Assembly

ABSTRACT In Salmonella, there are three classes of promoters in the flagellar transcriptional hierarchy. This organization allows genes needed earlier in the construction of flagella to be transcribed before genes needed later. Four operons (fliAZY, flgMN, fliDST, and flgKL) are expressed from both class 2 and class 3 promoters. To investigate the purpose for expressing genes from multiple flagellar promoters, mutants were constructed for each operon that were defective in either class 2 transcription or class 3 transcription. The mutants were checked for defects in swimming through liquids, swarming over surfaces, and transcriptional regulation. The expression of the hook-associated proteins (FlgK, FlgL, and FliD) from class 3 promoters was found to be important for swarming motility. Both flgMN promoters were involved in coordinating class 3 transcription with the stage of assembly of the hook-basal body. Finally, the fliAZY class 3 promoter lowered class 3 transcription in stationary phase. These results indicate that the multiple flagellar promoters respond to specific environmental conditions and help coordinate transcription with flagellar assembly.

scholarly journals ERCC6L2 Mutations Link a Distinct Bone-Marrow-Failure Syndrome to DNA Repair and Mitochondrial Function

2014 ◽  
Vol 94 (2) ◽  
pp. 246-256 ◽  
Author(s):  
Hemanth Tummala ◽  
Michael Kirwan ◽  
Amanda J. Walne ◽  
Upal Hossain ◽  
Nicholas Jackson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dna Repair ◽  
Mitochondrial Function ◽  
Bone Marrow Failure ◽  
Bone Marrow Failure Syndrome

scholarly journals Regulation of the CRISPR-Associated Genes by Rv2837c (CnpB) via an Orn-Like Activity in Tuberculosis Complex Mycobacteria

2018 ◽  
Vol 200 (8) ◽  
Author(s):  
Yang Zhang ◽  
Jun Yang ◽  
Guangchun Bai
Keyword(s):  
Transcriptional Regulation ◽  
Adaptive Immunity ◽  
Parent Strain ◽  
Tuberculosis Complex ◽  
Content Type ◽  
Multifunctional Protein ◽  
Type Iii ◽  
Associated Proteins ◽  
Cyclic Dinucleotides ◽  
Insight Into

ABSTRACT Clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-associated proteins (Cas) provide bacteria and archaea with adaptive immunity to specific DNA invaders. Mycobacterium tuberculosis encodes a type III CRISPR-Cas system that has not been experimentally explored. In this study, we found that the CRISPR-Cas systems of both M. tuberculosis and Mycobacterium bovis BCG were highly upregulated by deletion of Rv2837c ( cnpB ), which encodes a multifunctional protein that hydrolyzes cyclic di-AMP (c-di-AMP), cyclic di-GMP (c-di-GMP), and nanoRNAs (short oligonucleotides of 5 or fewer residues). By using genetic and biochemical approaches, we demonstrated that the CnpB-controlled transcriptional regulation of the CRISPR-Cas system is mediated by an Orn-like activity rather than by hydrolyzing the cyclic dinucleotides. Additionally, our results revealed that tuberculosis (TB) complex mycobacteria are functional in processing CRISPR RNAs (crRNAs), which are also more abundant in the Δ cnpB strain than in the parent strain. The elevated crRNA levels in the Δ cnpB strain could be partially reduced by expressing Escherichia coli orn . Our findings provide new insight into transcriptional regulation of bacterial CRISPR-Cas systems. IMPORTANCE Clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-associated proteins (Cas) provide adaptive immunity to specific DNA invaders. M. tuberculosis encodes a type III CRISPR-Cas system that has not been experimentally explored. In this study, we first demonstrated that the CRISPR-Cas systems in tuberculosis (TB) complex mycobacteria are functional in processing CRISPR RNAs (crRNAs). We also showed that Rv2837c (CnpB) controls the expression of the CRISPR-Cas systems in TB complex mycobacteria through an oligoribonuclease (Orn)-like activity, which is very likely mediated by nanoRNA. Since little is known about regulation of CRISPR-Cas systems, our findings provide new insight into transcriptional regulation of bacterial CRISPR-Cas systems.

scholarly journals The Nuclear Lamina: Protein Accumulation and Disease

Biomedicines ◽  
2020 ◽  
Vol 8 (7) ◽  
pp. 188
Author(s):  
Carla Almendáriz-Palacios ◽  
Zoe E. Gillespie ◽  
Matthew Janzen ◽  
Valeria Martinez ◽  
Joanna M. Bridger ◽  
...  
Keyword(s):  
Dna Repair ◽  
Protein Synthesis ◽  
Transcriptional Regulation ◽  
Nuclear Envelope ◽  
Genome Organization ◽  
Nuclear Lamina ◽  
Protein Accumulation ◽  
Protein Levels ◽  
Protein Clearance ◽  
Serious Disease

Cellular health is reliant on proteostasis—the maintenance of protein levels regulated through multiple pathways modulating protein synthesis, degradation and clearance. Loss of proteostasis results in serious disease and is associated with aging. One proteinaceous structure underlying the nuclear envelope—the nuclear lamina—coordinates essential processes including DNA repair, genome organization and epigenetic and transcriptional regulation. Loss of proteostasis within the nuclear lamina results in the accumulation of proteins, disrupting these essential functions, either via direct interactions of protein aggregates within the lamina or by altering systems that maintain lamina structure. Here we discuss the links between proteostasis and disease of the nuclear lamina, as well as how manipulating specific proteostatic pathways involved in protein clearance could improve cellular health and prevent/reverse disease.

scholarly journals GENE-41. UNDERSTANDING THE DIFFERENCES IN ADOLESCENT AND YOUNG ADULT (AYA) GLIOMAS AND OLDER ADULT (OA) GLIOMAS BASED ON FUNCTIONAL MOLECULAR SUBGROUPS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi106-vi106
Author(s):  
Catherine Bi ◽  
Ashwin Subramaniam ◽  
Joanne Xiu ◽  
Amy Heimberger ◽  
Sharon Michelhaugh ◽  
...  
Keyword(s):  
Dna Repair ◽  
Transcriptional Regulation ◽  
Tumor Suppressor ◽  
Metabolic Pathways ◽  
Tumor Suppressor Genes ◽  
Mutation Frequency ◽  
Pik3ca Mutation ◽  
Low Grade ◽  
Suppressor Genes ◽  
Pathway Gene

Abstract BACKGROUND Gliomas in the AYA population (15–39 years of age) have unique biological characteristics and need to be better characterized. METHODS Glioma tumors in AYA subjects and subjects >65 years of age (OA) were analyzed by next generation sequencing using a 592 gene panel. Pathogenic mutations were classified into five functional groups, viz. metabolic pathways genes (IDH1/2, FH), tumor suppressor genes (TP53, RB1, APC, NF1/2, PTEN, TSC1/2), genes involved in DNA repair (MMR genes, BRCA1/2, POLE, ARID1A, CHEK2, ATM, BLM, BRIP1, WRN, BARD1, POT1, MUTYH), oncogenes (BRAF, NRAS, HRAS, EGFR, PDGFRA, FGFR1, NOTCH1, MYCN), and genes involved in transcriptional regulation (SETD2, H3F3A, KMTD2A/2C/2D, KDM6A, PIK3CA). Mutation frequency in AYA tumors and OA tumors were compared using Chi-squared analysis (Pearson’s score χ2; likelihood ratio LR). RESULTS 720 unique gliomas tumors were analyzed: 118 AYA, 602 OA; 420 males, 300 females. When both groups are considered together, glioblastoma was the most common histology (75%), followed by grade 3 astrocytoma (13%), glioma NOS (3.8%), oligodendrogliomas (3%), low grade gliomas (2.9%) and other (2.3%). AYA tumors harbored more metabolic pathway gene mutations (χ2 137.7, p< 0.0001) driven primarily by IDH1 mutations, while OA tumors had a higher mutation frequency in oncogenes (χ2 9.22, p=0.0024) driven by EGFR mutations (LR 27.567) and tumor suppressor genes (χ2 40.35, p< 0.0001) driven by NF1 (LR 18.147) and PTEN (LR 66.216). No significant differences were noted in mutation frequency in DNA repair or transcriptional regulation genes. However, AYA glioblastoma tumors had a significant increase in mutations in genes involved in chromatin remodeling, (χ2 11.43, p=0.0007) even after excluding H3F3A. CONCLUSIONS Functional genomic classification of AYA tumors may help develop better targeted therapies, especially focused on genes involved in metabolic pathways and transcriptional regulation.

Helicobacter pylori infection affects mitochondrial function and DNA repair, thus, mediating genetic instability in gastric cells

2013 ◽  
Vol 134 (10) ◽  
pp. 460-466 ◽  
Author(s):  
Ana Manuel Dantas Machado ◽  
Claus Desler ◽  
Sisse Bøggild ◽  
Jesper A.B. Strickertsson ◽  
Lennart Friis-Hansen ◽  
...  
Keyword(s):  
Dna Repair ◽  
Helicobacter Pylori ◽  
Mitochondrial Function ◽  
Genetic Instability ◽  
Helicobacter Pylori Infection ◽  
Gastric Cells

scholarly journals Retroelement—Linked Transcription Factor Binding Patterns Point to Quickly Developing Molecular Pathways in Human Evolution

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 130 ◽  
Author(s):  
Daniil Nikitin ◽  
Andrew Garazha ◽  
Maxim Sorokin ◽  
Dmitry Penzar ◽  
Victor Tkachev ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Transcription Factor Binding ◽  
Molecular Pathways ◽  
Molecular Signaling ◽  
Regulatory Evolution ◽  
Factor Binding ◽  
Human Genes ◽  
Fatty Acids Metabolism ◽  
Cellular Immune

Background: Retroelements (REs) are transposable elements occupying ~40% of the human genome that can regulate genes by providing transcription factor binding sites (TFBS). RE-linked TFBS profile can serve as a marker of gene transcriptional regulation evolution. This approach allows for interrogating the regulatory evolution of organisms with RE-rich genomes. We aimed to characterize the evolution of transcriptional regulation for human genes and molecular pathways using RE-linked TFBS accumulation as a metric. Methods: We characterized human genes and molecular pathways either enriched or deficient in RE-linked TFBS regulation. We used ENCODE database with mapped TFBS for 563 transcription factors in 13 human cell lines. For 24,389 genes and 3124 molecular pathways, we calculated the score of RE-linked TFBS regulation reflecting the regulatory evolution rate at the level of individual genes and molecular pathways. Results: The major groups enriched by RE regulation deal with gene regulation by microRNAs, olfaction, color vision, fertilization, cellular immune response, and amino acids and fatty acids metabolism and detoxication. The deficient groups were involved in translation, RNA transcription and processing, chromatin organization, and molecular signaling. Conclusion: We identified genes and molecular processes that have characteristics of especially high or low evolutionary rates at the level of RE-linked TFBS regulation in human lineage.

Sign in / Sign up

Export Citation Format

Share Document