Researchers at Wellcome Trust Centre for Gene Regulation and Expression have made a significant discovery about how cells behave and protect themselves against cell death, cancers and genetic disorders. The team of Professor Tomo Tanaka and Dr Matt Renshaw at the Centre, working in collaboration with researchers in Germany and Japan, have discovered how cells ensure inheritance of their genetic information in order to prevent diseases.
They have uncovered what they described as 'clearing chromosome cling' in the crucial process of cell division, which generates the growth of tissue and organs. Human cells contain 46 chromosomes, all of which carry vital genetic information that is crucial for the proper function of cells. Chromosomes must be precisely copied and identical sets of chromosomes have to be distributed to newborn daughter cells upon cell division. Loss or excess of any chromosome could generate cancer cells, or cause genetic disorders such as Down's syndrome. To ensure the process of chromosome distribution, pairs of identical chromosomes cling together until their distribution. The research team has discovered how cells clear chromosome cling when chromosomes are distributed to daughter cells. They identified molecular 'winches' for chromosome recoiling that ensures this process. This finding uncovers a key cellular secret and gives an important insight to potential medical applications in the future.
Professor Tanaka explained why the discovery was important. 'Chromosome copying and distribution to daughter cells are both crucial processes,' he said. 'However, there is a time gap between the two, so cells need to mark each pair of identical chromosomes: a copy and its original, until the moment of their actual distribution to daughter cells. 'If this doesn't happen, identical chromosomes are mixed up with different ones, making it impossible to distribute individual copies of every chromosome to each daughter cell. 'Cells manage this process by gluing together a pair of identical chromosomes. However, this also means that the chromosome glue must be removed at the right time upon their separation to the daughter cells. If the removal is too early, cells lose an important mark for identical chromosomes. However, if it is too late, the distribution of chromosomes will not be properly completed.'
Dr Renshaw explained what they had discovered, saying, 'For removal of the chromosome glue, cells use special 'scissors' to cut it out. However, we have discovered that the glue still partly remains after use of the scissors and the pairs of chromosomes still cling together, and another mechanism must work to clear up the remaining chromosome cling. 'We found that, by recoiling stretched chromosomes, cells successfully breakup the chromosome cling and complete chromosome separation. We have also identified very efficient molecular winches that promote chromosome recoiling.'
The research team believes that this is one of the most crucial steps in assuring cells' chromosome inheritance during their divisions, thus potentially preventing cell death, cancers and other diseases. They are currently attempting to discover how these molecular winches are switched on at the right time in order to ensure chromosome separation. They hope that their discovery will help identify clues towards improving the diagnosis and treatment of diseases in the future. The team's findings have been published in the latest edition of the journal Developmental Cell.
The research has been funded by Human Frontier Science Program, Cancer Research UK, Medical Research Council, Lister Research Institute Prize, Biotechnology and Biological Sciences Research Council, and Wellcome Trust. Researchers at the European Molecular Biology Laboratory in Heidelberg, Germany and the Department of Biological Sciences at Osaka University in Japan have contributed to the research, which has taken place over the past four years.