Genome complexity: DNA repair system with p53 (Introduction)

by David Turell , Monday, September 26, 2016, 23:16 (2768 days ago) @ David Turell

DNA is under surveillance to check for incorrect copies as cells divide and copy DNA. p53 is a chemical which drives repair genes:-http://medicalxpress.com/news/2016-09-regulatory-rna-essential-dna-response.html-"researchers at the Stanford University School of Medicine have discovered a new player in this high-stakes molecular game in the form of a novel regulatory RNA they've named DINO. This RNA molecule binds to and stabilizes a well-known tumor suppressor protein called p53 that mobilizes a cell's response to DNA damage. When mutated, p53 is one of the most infamous bad guys in the cancer world.-"'It's so important for a cell to keep track of potentially dangerous changes to its genome," said professor of dermatology Howard Chang, MD, PhD. "But if cells reacted to every little ding, they would find themselves responding inappropriately—they would stop growing and maybe even self-destruct unnecessarily. You don't want to do this unless the DNA damage is severe. We've discovered that DINO is an integral part of this decision-making circuit."-***-"DNA damage is a natural byproduct of cell division because it is impossible to faithfully copy each of the 3 billion nucleotides that make up our genomes without making at least a few errors. Damage can also be caused by exposure to certain chemical agents, ultraviolet light and ionizing radiation.-"Most of the time these problems are recognized and quickly repaired by the cell. That's where p53 comes in. When it is doing its job, p53 recognizes and responds to DNA damage by increasing the expression of genes involved in DNA repair and cell division. In this way it functions as a tumor suppressor. When mutated, however, p53 loses its ability to modulate the cell's response to DNA damage. Mutations in p53 are among the most common causes of many types of cancer.-"Chang and his collaborators found that p53 also increases the expression of DINO. DINO, in turn, binds to and stabilizes p53 in a kind of positive feedback loop, amplifying its signal throughout the nucleus. (my bold)-***-"DINO is a member of a group of RNA molecules known as long noncoding RNAs, or lncRNAs. These molecules have been implicated in a growing number of critical regulatory roles throughout the cell. This is the first time that a lncRNA has been shown to be involved in this critical DNA damage-response pathway in living animals.
Chang and his colleagues found that when DINO expression is artificially increased, cells respond as if their DNA has been damaged even in the absence of any genome changes. In contrast, when DINO expression is inhibited, the cell responds less robustly to signals from p53.-
"'DINO expression allows the cell to fine-tune its response to DNA damage and respond appropriately," said Chang.-
"Because, as an RNA, DINO is made in the cell's nucleus where p53 is active, the researchers believe it may provide a more rapid and precise response to DNA damage than would a regulatory protein, which would be synthesized in the cytoplasm."-Comment: Another example of a feedback loop with automatic molecular actions. This had to be present from the beginning of life using DNA as the genome code, since copying DNA has to be closely monitored or life would not last. Saltation.