![]() ![]() Sara Sdelci at the premises of the Centre for Genomic Regulation, in Barcelona. If DNA damage occurs anyway, cells pause momentarily and carry out repairs, synthesizing new building blocks and filling in the gaps. Antioxidant enzymes are deployed to mop up reactive oxygen species at their source before they reach DNA, a defensive strategy that protects the roughly 3 billion nucleotides from suffering potentially catastrophic mutations. Just how buildings collapse from the cumulative effect of rust, reactive oxygen species threaten a genome’s integrity.Ĭells are thought to delicately balance their energy needs and avoid damaging DNA by containing metabolic activity outside the nucleus and within the cytoplasm and mitochondria. These reactions also create reactive oxygen species, dangerous by-products like hydrogen peroxide which damage the building blocks of DNA in the same way oxygen and water corrode metal and form rust. Credit: Sara Sdelci / CRGĪ typical human cell is metabolically active, roaring with chemical reactions that convert nutrients into energy and useful products that sustain life. The image illustrates the location of DNA damage (in the nucleus of these four cells – green) and the colocalization of PRDX1 (in red, same place). The findings can help guide future lines of cancer research by offering new clues to overcome drug resistance and eventually the design of new treatments. Cancer hijacks cellular metabolism for unfettered growth.The findings represent a paradigm shift because the nucleus has been historically considered to be metabolically inert, importing all its needs through supply chains in the cytoplasm.In a state of crisis, such as widespread DNA damage, the nucleus protects itself by appropriating mitochondrial machinery to carry out urgent repairs that threaten the genome’s integrity.The human nucleus is metabolically active, according to the findings of a new study in Molecular Systems Biology by researchers at the CRG in Barcelona and CeMM/Medical University of Vienna.The nucleus being metabolically active is a profound paradigm shift with implications for cancer research. In crisis, the nucleus calls antioxidant enzymes to the rescue. ![]() This shift in understanding of cellular metabolism can inform new strategies in cancer treatment, as cancer cells often hijack metabolic processes for their growth. This blog post is the first in a series that will track further progress on the ROP enhancement initiative.Researchers have discovered that a cell’s nucleus is metabolically active, with cellular enzymes moving to protect DNA integrity upon damage. A proposal to remove Section 71152 of the Inspection Procedure, for problem identification and resolution, was also raised at the meeting but was generally dismissed. As was stated at the public meeting, combining Columns 1 and 2 would be a long-term change. ![]() If the industry proposal prevails, it would mark a paradigm shift, considering Columns 1 and 2 have been in existence since the pilot program for ROP enhancement was introduced in 1999. Part of this proposal includes redefining labels for findings and combining Columns 1 and 2 of the Action Matrix. In 2018, the NRC solicited ideas for enhancing the ROP, which resulted in an industry proposal based on four points: US fleet maturity, improved safety margins, improved risk assessments, and greater use of risk-informed decisionmaking. The objectives of the ROP enhancement initiative are to evaluate whether the baseline inspection program remains relevant for the current environment, eliminate redundant or unnecessary inspection areas, maximize efficient and effective use of resources, and incorporate flexibility in program implementation, where appropriate. In January, the US Nuclear Regulatory Commission’s (NRC’s) staff hosted a public meeting with industry representatives to discuss the staff’s progress in reviewing recommendations for the NRC’s Reactor Oversight Process (ROP) framework enhancement initiative. ![]()
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