unexpected turn. The famous cancer gene BRCA1 may also play a role in neurodevelopmental disorders such as microcephaly ( right ), which causes small brain size.
PLoS Biol 2 (5): E134 (04)
The cancer gene BRCA1, that holds the breast tumors and ovarian at bay by producing proteins that repair damaged DNA, can also regulate brain size. Mice carrying a mutated copy of the gene were 10 times fewer neurons and other brain abnormalities, a new study suggests. These dramatic effects on the size and function of the brain is unlikely in humans holders of BRCA1 mutations, the authors of the study note, but they suggest the findings could shed light on the role of gene in brain evolution.
scientists have long known that the BRCA1 gene [estunesentinelleimportantecontrelesdommagesdel'ADNquipeuventconduireàdescancersdel'ovaireetduseinPlusdelamoitiédesfemmesayantunecopiemutéedu BRCA1 gene will develop breast cancer, a statistic that has led some who carry the mutation for preventive mastectomies. But his roles outside of the breast and ovaries are less clear, says Inder Verma, a geneticist and molecular biologist at the Salk Institute for Biological Studies in San Diego, California, who led the new study. mice bred without BRCA1 die soon after birth, it is clear that the gene is necessary to sustain life, but scientists are just beginning to unravel its many functions, he said. There
several years, one of the students in the lab noticed that Verma BRCA1 is very active in the neurectoderm, embryonic tissue tape containing neural stem cells that divide and differentiate into wide assortment of brain cell types and structures. Verma and his colleagues wondered why the gene was expressed at high levels in this region, and what would happen if it were eliminated. They created a strain of mice in which BRCA1 was eliminated only in neural stem cells. As the mice developed, Verma's team found that the brains of rodents were only a third of their normal size, with particularly striking reductions in brain areas involved in learning and memory. The cultured mice also had a wobbly gait-a drunk symptom of ataxia, a neurological disorder that affects muscle control and balance, the researchers report online today in Acts of national Academy of sciences .
Verma, member of laboratory Gerald Pao and colleagues sought to determine why the removal BRCA1 had caused these problems. Although neural stem cells divided at a normal rate, an unusually high number of dead cells soon after they formed, they found. The researchers also found that BRCA1 proteins were helping to keep the DNA of the erosion that the divided cells. Without BRCA induced DNA repair, a molecule called ATM kinase detected excessive DNA breakage and activated a chemical that kills damaged cells. Thus, mice with defective BRCA1 genes, many more cells were eliminated as would be destroyed in the normal brain development. Most of the cells that survived were disorganized and malformed, showing additional effects of defective DNA packaging, said Verma. Cellular disarray is similar to that observed in cancer, he said. "No orderly conduct" Both cancer cells and brain cells show
Verma is quick to point out that even if there were two case studies in which BRCA1 were linked to brain abnormalities mutations, dramatic effects documented in mice in the study are not likely to occur in women with BRCA1 mutation, which still have some functioning BRCA1 , compared to mice that had not.
Verma said the new data suggest that BRCA may have a role in the evolution of brain size. Genes involved in microcephaly, a condition in which patients have a brain about the size of chimpanzee brains, directly control the levels of BRCA1 expression, he said.
Jeremy Pulvers, a molecular biologist at the Max Planck Institute of Molecular and Cell Biology and Genetics in Dresden, Germany, where the company presented similar results in a previous article, says that the new study "provides a further proof that BRCA1 ... plays a specific role in brain size control. "" This is important fundamental basic science of how the genome is protected in rapidly proliferating cells in the brain "says Huda Zoghbi, a neuroscientist at Baylor College of Medicine in Houston, Texas.
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