Dna damage and repair mechanism

DNA repair is essential for cell vitality, cell survival, and cancer prevention, yet cells’ ability to patch up damaged DNA declines with age for reasons not fully understood. Now, research led by scientists at Harvard Medical School (HMS) reveals a critical step in a molecular chain of events that allows cells to mend their broken DNA. The findings, to be published March 24 in Additionally, experiments conducted in mice show that treatment with the NAD precursor NMN mitigates age-related DNA damage and wards off DNA damage from radiation exposure. The scientists caution that the effects of many therapeutic substances are often profoundly different in mice and humans owing to critical differences in biology. However, if affirmed in further animal studies and in humans, the findings can help pave the way to therapies that prevent DNA damage associated with aging and with cancer treatments that involve radiation exposure and some types of chemotherapy, which, along with killing tumors, can cause considerable DNA damage in healthy cells. Human trials with NMN are expected to begin within six months, the researchers said. “Our results unveil a key mechanism in cellular degeneration and aging, but beyond that they point to a therapeutic avenue to halt and reverse age-related and radiation-induced DNA damage,” said senior author A previous study led by Sinclair showed that NMN reversed muscle aging in mice. A plot with many characters The investigators started by looking at a ca...

Repairing damage in DNA from anything that causes a mutation, such as UV radiation and tobacco smoke, is a fundamental process that protects our cells from becoming cancerous. In the study published in the journal Nature, the scientists analysed more than 20 million DNA mutations from 1,161 tumours across 14 cancer types. They found that in many cancer types, especially skin cancers, the number of mutations was particular high in regions of the genome known as 'gene promoters'. Significantly, these DNA sequences control how genes are expressed which in turn determine cell type and function. The researchers showed that the numbers of DNA mutations are increased in gene promoters because the proteins that bind DNA to control gene expression block one of our cell repair systems responsible for fixing damaged DNA. This system is known as nucleotide excision repair (NER) and is one of a number of DNA repair mechanisms that occurs in human cells and the only one capable of repairing damage from UV light. Lead author of the study Dr Jason Wong, group leader of Bioinformatics and Integrative Genomics at UNSW's Lowy Cancer Research Centre, said the results provide compelling evidence that increased mutations at gene promoter sites are caused by a compromised NER system. "What this research also tells us is that while the human body is pretty good at repairing itself, there are certain parts of our genome that are poorly repaired when we sustain damage from mutagens such as UV light...

Our DNA is like a library - found in the nucleus of our cells - with thousands of books. Some of these books - called genes - are extremely important, because they carry the recipes for every single protein found in the cell. Now, on a molecular level, DNA is made up of two strands of Nucleotides of DNA are made out of a sugar - deoxyribose, a phosphate, and one of the four nucleobases - adenine, cytosine, guanine, and thymine - or, A, C, G, T for short. The Now, the goal of DNA is to store information and pass it onto their daughter cells, and to use this information to create proteins. To do this, there are two critical processes - So, the If we zoom onto the double- stranded DNA, we can see that during Then another enzyme, DNA polymerase, uses each of the single strands as a template and adds complementary Gene expression, on the other hand, is the process of decoding the information stored in the DNA in order for the cell to make proteins, and it includes

Summary points • 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, • In a state of crisis, such as widespread DNA damage, the nucleus protects itself by appropriates mitochondrial machinery to carry out urgent repairs that threaten the genome's integrity • 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 • Cancer hijacks cellular metabolism for unfettered growth. 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 Main text A typical human cell is metabolically active, roaring with chemical reactions that convert nutrients into energy and useful products that sustain life. 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. Just how buildings collapse from the cumulative effect of rust, reactive oxygen species threatens a genome's integrity. Cells 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. Antioxidant enzymes are deployed to mop up...

• • DNA damage and repair articles from across Nature Portfolio Definition DNA damage and repair refers to the creation and correction of DNA lesions that threaten genome integrity. Because DNA replication errors or environmental agents that damage DNA can introduce mutations if not corrected, multiple cellular DNA repair mechanisms exist to remove damaged regions of chromosomes to prevent these potentially deleterious effects. In the DNA damage response, ADP-ribosylation is an essential signaling pathway. Here the authors utilize a multidisciplinary approach to establish its molecular basis in fruit flies and provide evidence for Drosophila’s suitability as model organism. • Pietro Fontana • , Sara C. Buch-Larsen • & Ivan Ahel The enzymatic activity of PARP1—which adds chains of (poly-ADP)-ribose (PAR) to proteins—initiates DNA repair by leading to more-accessible chromatin and recruitment of PAR-dependent DNA-repair proteins. New work shows that these PARP1-catalysed functions are redirected by the auxiliary factor HPF1 in cells. • Johannes Rudolph • & Karolin Luger