Hotspots found for chromosome gene swappingNovember 30, 2007Crossovers and double-strand DNA breaks do not occur randomly on yeast chromosomes during meiosis, but are greatly influenced by the proximity of the chromosome's telomere, according to research in the laboratory of Whitehead Fellow Andreas Hochwagen. This work may lead to a better understanding of developmental chromosome abnormalities and birth defects. Meiosis is a type of cell division that produces cells with only one copy of each chromosome-spores in yeast, and eggs and sperm in higher organisms. During meiosis, chromosome pairs line up in the middle of the cell. The chromosome pairs are then pulled apart, with complete copies of all of the chromosomes ending up at opposite sides of the cell. To ensure that the chromosomes align properly in the middle of the cell, the chromosomes crossover-swap certain sections of genes. Without the crossovers, the chromosomes could misalign and both copies of a chromosome could end up in one cell. When this happens, the cells die or suffer from severe genetic problems, such as Down syndrome. Before a crossover can occur at a given site, both strands of a chromosome's DNA helix must be broken. About half of these double-strand DNA breaks (DSBs) are processed to form crossovers, and the rest are resealed to restore the original chromosomes. The final number of crossovers is relatively small and scientists have long wondered how cells ensure that even the smallest chromosomes undergo at least one crossover. Indeed, in almost half of Down's Syndrome cases, chromosome 21, one of the smallest human chromosomes, failed to form a crossover in one of the parents. In a paper published online in Current Biology on November 29, Massachusetts Institute of Technology graduate student Hannah Blitzblau suggests that part of the answer lies in where DSBs are formed. Blitzblau has shown that these DSBs are not scattered randomly throughout the chromosomes, but occur most frequently in a specific band near telomeres, the end caps of chromosomes. When telomeres are spliced into the central part of a chromosome, this DSB "hotspot" effect is still seen at the same distance from the new telomeres. "This is a simple mechanism for making sure that all chromosomes, even the shortest ones, have the crossovers required for meiosis," says Blitzbau. "If the breaks occurred randomly, the smallest chromosomes often wouldn't have any crossovers." In addition, Blitzblau showed that DSBs occur at high rates around the central part of the chromosome called the centromere, It was previously thought that DSBs and crossovers rarely occurred in this region. "This is incredibly surprising," says Hochwagen. "The chromosomes start the crossover process in the centromeres, but divert and reseal the breaks instead." Some of the earlier research had been done in mutant yeast strains; the Whitehead researchers say that the current work in non-mutant yeast is a more accurate representation of normal processes. This research will help scientists understand chromosome events leading to infertility and birth defects. In addition, although this work does not touch on why some cells divide improperly, Blitzblau and Hochwagen anticipate that the technologies developed for this study will allow researchers to identify sites that are sensitive to breaks caused by agents, such as certain cancer drugs. The investigators are adapting the methods used in yeast to map break-sensitive sites in mammalian cells. Whitehead Institute for Biomedical Research |
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| Related Chromosomes Current Events and Chromosomes News Articles Possible Link Studied Between Childhood Abuse and Early Cellular Aging Children who suffer physical or emotional abuse may be faced with accelerated cellular aging as adults, according to new research from Butler Hospital and Brown University. Scientists at UA, collaborating institutions decode maize genome Scientists from the University of Arizona led by Arizona Genomics Institute director Rod A. Wing and from collaborating institutions have deciphered the complete genetic code of the maize plant for the first time. New map of variation in maize genetics holds promise for developing new varieties A new study of maize has identified thousands of diverse genes in genetically inaccessible portions of the genome. New techniques may allow breeders and researchers to use this genetic variation to identify desirable traits and create new varieties that were not easily possible before. New Maize Map to Aid Plant Breeding Efforts In a massive survey of genetic diversity in maize, also known as corn, researchers across the United States, have developed a gene map that should pave the way to significant improvements in a plant that is a major source of food, fuel, animal feed and fiber around the world. Chromosomes dance and pair up on the nuclear membrane Meiosis - the pairing and recombination of chromosomes, followed by segregation of half to each egg or sperm cell - is a major crossroads in all organisms reproducing sexually. Largest gene study of childhood IBD identifies 5 new genes In the largest, most comprehensive genetic analysis of childhood-onset inflammatory bowel disease (IBD), an international research team has identified five new gene regions, including one involved in a biological pathway that helps drive the painful inflammation of the digestive tract that characterizes the disease. NIH-funded researchers transform embryonic stem cells into human germ cells Researchers funded in part by the National Institutes of Health have discovered how to transform human embryonic stem cells into germ cells, the embryonic cells that ultimately give rise to sperm and eggs. A solution to Darwin's 'mystery of the mysteries' emerges from the dark matter of the genome Biological species are often defined on the basis of reproductive isolation. Ever since Darwin pointed out his difficulty in explaining why crosses between two species often yield sterile or inviable progeny (for instance, mules emerging from a cross between a horse and a donkey), biologists have struggled with this question. Common weed could provide clues on aging and cancer A common weed and human cancer cells could provide some very uncommon details about DNA structure and its relationship with telomeres and how they affect cellular aging and cancer, according to a team led by scientists from Texas A&M University and the University of Cincinnati (UC). CSHL-led team discovers rare mutation dramatically increasing schizophrenia risk An international team of researchers led by geneticist Jonathan Sebat, Ph.D., of Cold Spring Harbor Laboratory (CSHL), has identified a mutation on human chromosome 16 that substantially increases risk for schizophrenia. More Chromosomes Current Events and Chromosomes News Articles |
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