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RNasi H2, the protein that “cuts” DNA errors

A research group of the Department of Life Sciences of the University of Milan has identified the protein which guides the repair mechanism of DNA replication errors and which, if altered, is linked to the development of several types of cancer.
When tissues, organs and ultimately an organism stemming from one fertilized egg cell are formed, genetic information contained in its DNA are completely duplicated and then transmitted faithfully from the parent cell to offspring cells.
In order for this to occur, the DNA copying process must be extremely precise. This is made possible thanks to the high fidelity of the DNA replication mechanism and to a specific repair mechanism called mismatch repair which identifies any errors and corrects them.
Alterations of the mismatch repair cause a genetic predisposition for colorectal cancer, also known as Hereditary Non Polyposis Colon Cancer (HNPCC), but also other kinds of tumours.
But how do mismatch repair proteins manage to distinguish between correct and incorrect DNA information in men and women the Life Sciences Department research group of the University of Milan, coordinated by Marco Muzi Falconi, Paolo Plevani and Federico Lazzaro and financed by the Italian Association of Research on Cancer (AIRC), Telethon and The Ministry of Education, Universities and Research (MIUR), collaborated with the University of Zurich in trying to find an answer to this question.
The conclusions of their research were published in the prestigious journal Molecular Cell . By combining human cells and yeast, the researchers identified a mechanism which instructs the mismatch repair proteins on how to repair errors. A protein called RNasi H2 plays a pivotal role in this process as it cuts the DNA near the error to allow the mismatch repair protein to remove the wrong information and substitute it with correct information.
This discovery could have a significant impact on the research of new anti-cancer drugs and for the development of new chemotherapeutic strategies. But the study also opens prospects in another direction: the poor functioning of RNasi H2 protein causes a genetic pathology known as the Aicardi-Goutières Syndrome (AGS), a disorder of which the pathogenesis still unknown. Further studies could therefore ascertain whether the process which has been identified by this recently published study is connected to the onset of AGS.            

14 June 2013
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