RESUMO
The first centromeric protein identified in any species was CENP-A, a divergent member of the histone H3 family that was recognised by autoantibodies from patients with scleroderma-spectrum disease. It has recently been suggested to rename this protein CenH3. Here, we argue that the original name should be maintained both because it is the basis of a long established nomenclature for centromere proteins and because it avoids confusion due to the presence of canonical histone H3 at centromeres.
Assuntos
Autoantígenos/genética , Proteínas Cromossômicas não Histona/genética , Histonas/genética , Autoantígenos/metabolismo , Centrômero , Proteína Centromérica A , Proteínas Cromossômicas não Histona/metabolismo , Histonas/metabolismo , Humanos , Cinetocoros , Escleroderma Sistêmico/genética , Terminologia como AssuntoRESUMO
Eukaryotic systems self-organise by using molecular railways to shuttle specific sets of molecular components to specific locations. In this way, cells are enabled to become larger, more complex and more varied, subtle and effective in their activities. Because of the fundamental importance of molecular railways in eukaryotic systems, understanding how these railways work is an important research goal. Mechanochemical cell biology is a newly circumscribed subject area that concerns itself with the molecular and cell biological mechanisms of motorised directional transport in living systems.
Assuntos
Biologia Celular , Técnicas Citológicas/métodos , Animais , Humanos , Modelos Biológicos , Estresse MecânicoRESUMO
In eukaryotic cells, surveillance mechanisms detect and respond to DNA damage by triggering cell-cycle arrest and inducing the expression of DNA-repair genes [1]. In budding yeast, a single DNA double-strand break (DSB) is sufficient to trigger cell-cycle arrest [2]. One highly conserved pathway for repairing DNA DSBs is DNA non-homologous end-joining (NHEJ), which depends on the DNA end-binding protein Ku [3]. NHEJ also requires the SIR2, SIR3 and SIR4 gene products [4] [5], which are responsible for silencing at telomeres and the mating-type loci [6]. Because of the link between NHEJ and the Sir proteins, we investigated whether DNA damage influences telomeric silencing. We found that DNA damage triggers the reversible loss of telomeric silencing and relocation of Sir3p from telomeres. Complete Sir3p relocation was triggered by a single DNA DSB, suggesting that the singal is amplified. Consistent with this idea, Sir3p relocation depended on the DNA damage-signalling components Ddc1p and Mec1p. Thus, signalling of DNA damage may release Sir3p from telomeres and permit its subsequent association with other nuclear subdomains to regulate transcription, participate in DNA repair and/or enhance genomic stability by other mechanisms.
Assuntos
Ciclo Celular/fisiologia , Dano ao DNA , Reparo do DNA/fisiologia , DNA Fúngico/metabolismo , DNA/metabolismo , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/fisiologia , Histona Desacetilases , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/fisiologia , Proteínas Reguladoras de Informação Silenciosa de Saccharomyces cerevisiae , Telômero/metabolismo , Transativadores/metabolismo , Bleomicina/toxicidade , Cromossomos Fúngicos/efeitos dos fármacos , Cromossomos Fúngicos/metabolismo , Cromossomos Fúngicos/ultraestrutura , DNA/genética , Reparo do DNA/genética , DNA Fúngico/genética , Proteínas de Ligação a DNA/fisiologia , Genes Reporter , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas Serina-Treonina Quinases , Proteínas Recombinantes de Fusão/biossíntese , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Sirtuína 2 , Sirtuínas , Telômero/efeitos dos fármacos , Telômero/ultraestrutura , Transativadores/fisiologiaRESUMO
The alpha(1) subunit provides both the voltage-sensing mechanism and the ion pore of voltage-dependent calcium channels. Of the six classes of alpha(1) subunit cloned to date, alpha)1A) is the subject of debate in terms of its functional correlate, although it is generally thought to encode voltage-dependent calcium channels of the omega-agatoxin IVA-sensitive, P/Q type. In the present study, an alpha(1A)-specific riboprobe and antibody were used with in situ hybridisation and immunohistochemical techniques to localise alpha(1A) messenger ribonucleic acid transcripts and subunit protein throughout the mature rat brain. Dual localisation of alpha(1A) protein and markers for acetylcholine, catecholamines, and 5-hydroxytryptamine have also been performed in a number of discrete areas. Abundant and widespread distribution of alpha(1A) protein was found, with immunoreactivity occurring both in cell bodies and as punctate staining in areas of neuronal processes. Several associations were noted across alpha(1A) localisation, defined neuroanatomical regions, and neurotransmitter systems. However, alpha(1A) expression was not confined to loci corresponding to any one neurotransmitter type, although a high level of expression was observed in cholinergic neurones. The distribution of the alpha(1A) subunit in the rat corresponded well with the limited human mapping data that are available.
