Impaired DNA demethylation of C/EBP sites causes premature aging

Evidence that protein binding specifies sites of DNA demethylation.

It has been hypothesized that protein factors may protect CpG islands from methyltransferase during development and that demethylation may involve protein-DNA interactions at demethylated sites. However, direct evidence has been lacking. In this study, demethylation at the EBNA-1 binding sites of the Epstein-Barr virus latent replication origin, oriP, was investigated by using human cells. Seve...

DNA demethylation.

Cytosine 59 methylation of CpG dinucleotides within and around genes exerts a major influence on transcription in many plants and animals (1–3). DNA methylation can be causal for transcriptional silencing (4–5) and targets the machinery necessary to assemble specialized chromatin enriched in deacetylated histones (6–8). Once established in somatic cells, CpG methylation patterns within the geno...

Transcriptional Functions of DNA Repair Proteins Involved in Premature Aging

Premature aging diseases or progerias are rare genetical disorders displaying symptoms of the aging body early in life or even in childhood. They are called segmental because they show some, but not all features of aging. There is the progeria of the adult, Werner syndrome and, more severe because limiting lifespan to the first or second decade, the progerias of the childhood, Cockayne syndrome...

Transcriptional Functions of DNA Repair Proteins Involved in Premature Aging

Therapeutic and space radiation exposure of mouse brain causes impaired DNA repair response and premature senescence by chronic oxidant production

Despite recent epidemiological evidences linking radiation exposure and a number of human ailments including cancer, mechanistic understanding of how radiation inflicts long-term changes in cerebral cortex, which regulates important neuronal functions, remains obscure. The current study dissects molecular events relevant to pathology in cerebral cortex of 6 to 8 weeks old female C57BL/6J mice t...