Fungi - Candida albicans - Research News, Data, Publications & Aproaches - ERG11 Mutations - Telomeres - Sub-Telomeric Structures - Chromatin Landscape - Nuclear Biology & Nuclear Chemistry Aproaches - Redox–Chromatin Coupling - Non-Elaborate Posts - Post 2


At the biochemical heart of this coupling lies NAD⁺, a redox cofactor that doubles as a substrate for sirtuin deacetylases. In C. albicans, Sir2p and Hst1p catalyze histone deacetylation, using NAD⁺ to remove acetyl groups from lysine residues on histone tails. This reaction not only modifies chromatin structure but consumes NAD⁺, linking gene silencing to metabolic oxidation states. When the NAD⁺/NADH ratio declines — for instance, during oxidative stress or mitochondrial dysfunction — sirtuin activity diminishes, loosening chromatin and derepressing subtelomeric genes such as ERG11. Thus, a single redox couple dictates epigenetic accessibility, allowing the chemical state of the cell to sculpt transcriptional landscapes in real time.

Comments

Post a Comment

Popular posts from this blog

   At the biochemical level, ERG11 ’s function as a heme-dependent monooxygenase interlocks with the cell’s oxidative balance. Heme fluctuations within the nucleus can alter the activity of heme-responsive transcription factors and chromatin modifiers, introducing a chemical feedback loop between metabolism and genetic variation (Puig & Gutiérrez, 2022). Reactive oxygen species generated by azole stress promote DNA oxidation and base substitution events preferentially within open chromatin domains. This coupling of redox chemistry with mutation formation constitutes a nuclear-scale biochemical evolution engine—one where chemical disequilibrium catalyzes genomic diversity in real time.
Read more

Fungi - Candida auris - Non-Elaborate Posts - Post 2

Genetics and genetic mutations for resistance to fluconazole ERG11 mutations (notably Y132F, K143R) are common contributors to fluconazole resistance; and Cas9 editing showed direct contribution of these alleles to elevated MICs. Additional determinants (TAC1B, efflux pumps, aneuploidy) amplify resistance. Different geographic clades show distinct ERG11 allele frequencies. Genome assemblies reveal structural variation and copy-number differences Resistance evolves under strong antifungal selection in hospitals. Surveillance sequences help track clonal spread and mutation patterns
Read more
In some settings, susceptible-dose dependent (SDD) categorization is used: isolates with intermediate MICs may still respond to higher fluconazole doses, but the presence of ERG11 mutations often reduces the likelihood of clinical success even with dose escalation. ( PMC ) Beyond single substitutions, clinical isolates frequently carry combinations of ERG11 changes plus efflux-regulatory mutations (e.g., TAC1 gain-of-function) that together produce higher MICs and poorer outcomes; thus, sequencing plus expression data can refine prognostic interpretation.
Read more