Cyclin E, which was also found to associate with Orc1, is known to be required for centriole and centrosome duplication and also stimulates the duplication of DNA in chromosomes. This protein is found at high levels in cells at the start of the division cycle and helps cells make one copy of their DNA.īut a related protein called Cyclin E may be the target of Orc1. They suggest that Orc1 is ferried to the centrosomes by the action of a protein known as Cyclin A. This function of Orc1 depends on its ability to physically associate with the centrosomes, the researchers showed. In cells that lacked Orc1, the CSHL scientists found that the centrioles were “disengaged” from the original, suggesting that Orc1 might prevent re-duplication by helping the new centrosomes to stay connected to the old. Stillman’s team hypothesizes that it is this “engagement” of the paired centrioles that stops the original centriole pair from duplicating. Upon the cell’s commitment to cell division, however, the centriole pair is duplicated to produce two new centriole pairs this occurs precisely as copying of the chromosomes gets under way. Before a pair is copied, the two centrioles normally stay connected to each other. Stillman’s laboratory found that Orc1 also controls the number of centrioles in a cell.
These duplicate during cell division to produce two centriole pairs. Within each centrosome are a pair of tiny machines called centrioles. Orc1 forces new centrosomes to stay in touch The CSHL team found that a shortened version of Orc1 that lacked the ability to start DNA duplication was still able to limit centrosome copying to once per cell-division cycle. This new role for Orc1 seems to be separate from its duties in helping cells copy DNA. It was thus deduced that Orc1 allows cells to duplicate centrosomes once per division cycle, but prevents centrosomes from being re-duplicated. Loss of Orc1 alone, the scientists found, spurred cells to accumulate excess centrosomes.Ĭells that were induced to produce more Orc1, on the other hand, had the normal amount of centrosomes, even when centrosomes were induced to re-duplicate via drug treatment of cells. They blocked the production of each of the proteins that combine to form ORC in human cells. To investigate which of the ORC proteins limit centrosome copying, Stillman and co-investigators Adriana Hemerly, Supriya Prasanth and Khalid Siddiqui, used RNA interference, or RNAi, a technique that uses small pieces of RNA to shut off specific genes. Recently it had become clear that some ORC proteins might be doing more than jump-starting DNA duplication the accumulation of extra centrosome copies in cells that lack ORC suggested that some or all ORC proteins might play a role in centrosome duplication as well. ORC, as it is called, is an assembly that attaches to particular sequences within all the DNA in the cell and prepares it for duplication.
Stillman and his colleagues to control centrosome duplication is Orc1, one of six proteins that comprise the Origin Recognition Complex. Their findings will appear in the February 6th issue of the journal Science. They have identified a protein molecule that controls the copying of the centrosome in human cells and prevents it from being re-duplicated. Hence the importance of new research by Professor Bruce Stillman, Ph.D., and his lab group at Cold Spring Harbor Laboratory (CSHL). Extra copies can result in incorrect distribution of chromosomes, which can lead to genomic instability and cancer. It’s crucial that cells duplicate their centrosome only once during each division cycle. By pulling on the chromosomes, the spindles separate them into two sets, each divided equally into the two emerging daughter cells. Each centrosome serves as an anchor for a spindle, a complex structure of filament-like tubules that radiates out from each centrosome and connects with special sites called centromeres on the chromosomes.
The two new sets of chromosomes then have to be separated from one another and correctly distributed to the resulting “daughter” cells, so that both daughter cells are genetically identical to the original, or “parent,” cell.ĭuring cell division, a cellular organ called the centrosome, and a copy of the centrosome, position themselves at opposite ends of the dividing cell. Team finds that Orc1, part of machinery that initiates DNA replication, prevents excess centrosome duplicationīefore a cell can divide into two, first it must duplicate its genetic material–the DNA packed in its chromosomes.
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