Baylor School of Medicine: using bacteria to find people who can cause DNA damage and promote cancer

The team, led by researchers at Baylor medical school and the University of Texas at Austin, used an unconventional approach to using bacteria to find human proteins that can cause DNA damage and promote cancer The study, reported in the journal Cell, also suggests the biological mechanism by which these proteins can damage DNA, opening up the possibility for future cancer treatment
"Our cells produce protein carcinogens," said Dr Susan M Rosenberg, chair of cancer research at Ben F love, Professor of molecular and human genetics and co-author of molecular virology and Microbiology and Baylor's Journal of Biochemistry and molecular biology "Cancer is a mutated disease Normal cells that accumulate several mutations in a particular gene are likely to become cancer cells " Mutations that cause cancer may be the result of DNA damage External factors such as tobacco smoke and sunlight can damage DNA, but most DNA damage seems to be caused by events within cells and mediated by cell components (including proteins) Although these events are important, they have not been extensively studied "One way that proteins can cause DNA damage is by overproduction, which is a relatively frequent cellular event," said Rosenberg, who is also director of the cancer evolution program at Baylor Dan l Duncan comprehensive cancer center "In this study, we began to find proteins that, when over produced by cells, damage DNA in a way that leads to cancer." In order to reveal these DNA "damaged" proteins, the researchers used an unconventional method They looked at proteins to search for proteins that promote DNA damage in human cells, which, when overproduced, causes DNA damage in bacterial Escherichia coli "Although bacteria are different from humans, their basic biological processes are similar, so we think that through this approach we may find common mechanisms of DNA damage that may be related to cancer," Rosenberg said "It's a crazy idea," Rosenberg said It's also possible with the support of two sources of funding designed to try high-risk strategies If successful, it will have a big impact: the 16 person experimental team received the Pioneer Award from the president of the National Institutes of health, the WM Keck foundation, and many other grants E.coli revealed a new candidate for cancer promoting protein The researchers genetically engineered the bacteria to glow red when DNA is destroyed They then overexpressed each of the 4000 genes present in E coli and determined which genes make the bacteria glow red "We found a wide and diverse network of proteins that, when overproduced, alter cells in ways that cause DNA damage," Rosenberg said "As expected, some of these proteins are involved in DNA processing or repair, but surprisingly, most of them are not directly related to DNA For example, some DNA damage proteins are involved in the transport of molecules on the cell membrane When researchers looked for human protein relatives whose DNA "damaged" proteins they found in bacteria, they found 284 Interestingly, they determined that these human proteins were more relevant to cancer than random proteomes In addition, protein RNA (an indicator of protein production) predicted the mutation of tumor and poor prognosis of patients When researchers overproduce these proteins in human cells in the laboratory, half of them cause DNA damage and mutations "We found that E coli can help identify DNA damage proteins and mechanisms of action in human cells quickly and cheaply "Some proteins and their mechanisms are known to be associated with cancer, but many others are not suspected of being on the list of carcinogens," said Dr Christophe Herman, Professor of molecular and human genetics, molecular virology and microbiology, Baylor medical school, member of the Dan l Duncan comprehensive cancer center and co-author "I think the way to recognize that DNA can be destroyed is very special This study opens up new ways to develop new mechanisms to protect our genomes and how their dysfunction can change our DNA integrity and lead to cancer, "said Dr Kyle M Miller, associate professor of Biological Sciences at the University of Texas at Austin and a member of Baylor's Dan l Duncan comprehensive cancer center and co-author "This is another example of the power of model biology to discover the fundamental biological processes that can reveal how human cells and cancer work." "Our work is of great significance in both basic biology and clinical research," Rosenberg said "We offer a previously unknown understanding of the various mechanisms of DNA damage that can lead to cancer In the future, the discovery could lead to new ways to identify people who may have cancer in order to develop strategies to prevent it, slow it down or catch it early " Two co authors of the study were doctoral students: Dr Jun Xia of Baylor School of medicine and Dr Liya Chiu of the University of Texas at Austin.