RESUMEN
Nucleoli, the largest subnuclear compartments, are formed around arrays of ribosomal gene repeats transcribed by RNA polymerase I. The primary function of nucleoli is ribosome biogenesis. Specific DNA damage response mechanisms exist to maintain the genomic stability of ribosomal repeats. Here, we provide a snapshot of our current understanding of processes involved in nucleolar DNA damage response. We discuss structure and function of ribosomal repeats, techniques developed for studying DNA damage response in nucleoli, as well as molecular mechanisms of DNA damage-induced repression of nucleolar transcription and nucleoli reorganization.
Asunto(s)
Nucléolo Celular , Inestabilidad Genómica , Nucléolo Celular/genética , Daño del ADN , ADN Ribosómico , Humanos , ARN Ribosómico , RibosomasRESUMEN
Reactions of genetically identical cells to various exogenous and endogenous stimuli can vary significantly. One of the main factors of this non-genetic cellular heterogeneity is the cell cycle. The most convenient way to study the subcellular processes depending on the cell cycle stage is the synchronization of the cells. Toxic inhibitors of DNA replication and/or mitotic spindle assembly are typically used to synchronize cells. It is important to accurately select the synchronization method for a particular experiment. In this study, we performed a comparative analysis of the synchronization methods of normal and transformed human cells, paying special attention to the accuracy of synchronization and toxicity of the methods used.
Asunto(s)
Ciclo Celular , Replicación del ADN , Línea Celular Transformada , Humanos , Mitosis , Huso AcromáticoRESUMEN
Heat stress is one of the most popular models for studying the regulation of gene expression. For decades, researchers' attention was focused on the study of the mechanisms of transcriptional activation of stress-induced genes. Although the phenomenon of heat stress-induced global transcriptional repression is known for a long time, the exact molecular mechanisms of such a repression are poorly explored. In this mini-review, we attempt to summarize the existing experimental data on heat stress-induced transcriptional repression.
Asunto(s)
Respuesta al Choque Térmico/genética , Transcripción Genética/fisiología , Animales , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Calor , Regiones Promotoras Genéticas , Activación TranscripcionalRESUMEN
Using indirect immunofluorescence, in this study we showed that the constitutive heat shock protein HSC70 forms granule-like structures in the cytoplasm of human cells several days after the exposure to heat stress. It was shown that this effect is not the result of HSC70 overexpression under heat stress and is not due to the formation of hyperthermia-induced translational stress granules in the cytoplasm.
Asunto(s)
Gránulos Citoplasmáticos/metabolismo , Proteínas del Choque Térmico HSC70/metabolismo , Respuesta al Choque Térmico , Humanos , Células MCF-7 , Factores de TiempoRESUMEN
Although the heat-stress response has been extensively studied for decades, very little is known about its effects on nucleic acids and nucleic acid-associated processes. This is due to the fact that the research has focused on the study of heat shock proteins and factors (HSPs and HSFs), their involvement in the regulation of transcription, protein homeostasis, etc. Recently, there has been some progress in the study of heat stress effects on DNA integrity. In this review, we summarize and discuss well-known and potential mechanisms of formation of various heat stress-induced DNA damage.