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Ataxia-telangiectasia mutated (ATM) is best known for its role in orchestrating the DNA damage response in response to double-strand breaks. However, it is now emerging that it is a far more versatile kinase, with roles in cell responses to other genotoxic stresses and in signalling pathways involved in cellular homeostasis.
The ability of signal transduction pathways to directly modify chromatin provides a means for rapid, and potentially long-lived, responses to environmental cues. Understanding how these modifications are stored on chromatin, integrated and interpreted should provide insight into the short- and long-term control of gene expression.
During cell reprogramming and direct cell fate conversion, changes in somatic and pluripotent cell fates do not require the passage through a hierarchy of distinct cell fates that are proposed to occur during normal development and are consistent with the original Waddington model. Instead, a 'flat epigenetic disc' model might explain cell fate transitions during these processes.
All three domains of life – Bacteria, Archaea and Eukarya – have a proteostasis network that modulates protein folding in response to changes in the environment and to genetic variation. This proteostasis network has co-evolved with the proteome and is thought to play a part in driving evolution.
Transcription-independent diffusible damage signals, such as Ca2+, H2O2and ATP, are generated immediately after epithelial wounding to alert tissues to damage. Together, these signals have short-term effects on actomyosin structures and immune cell chemotaxis, and in the longer term coordinate the subsequent transcription of specific wound response genes to direct the wound healing process.