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Open Access Elucidation of the Mechanism Regulating Transcription Associated Dna Double Strand Break Repair and Its Pathway

The ability to repair breaks and mutations in DNA is essential for a cell's – and therefore organism's – survival. Breaks and other mutations arise naturally over time and are dealt with by the cell using several different pathways. Incorrect or non-existent DNA repair can lead directly to either cell death or the development of a cancerous cell. A break in double strand in the DNA is particularly serious. Dr Atsushi Shibata, a Principle Investigator and Senior Lecturer at Gunma University, Japan explains that the cell has two key ways to deal with this sort of break. 'These are homologous recombination repair (HRR) and non-homologous end-joining (NHEJ),' he says. 'HRR is the more accurate pathway, while NHEJ provides a quicker fix, but it has a risk of error under some circumstance.' This makes HRR perfectly suited to repairing important parts of the genome whilst NHEJ is better suited to less key regions.
The molecular mechanisms behind these repair pathways have been extensively studied. However, the question of how a particular pathway is selected over another in different situations is less well characterised, particularly in human normal cells as well as cancer cells. Uncovering the signalling pathways behind this choice the cell makes is both very important to our fundamental understanding of DNA repair and to its potential use in tackling cancer. Investigating these pathways Shibata is collaborating with Dr Takaaki Yasuhara from the University of Tokyo. They have revealed some of the inner workings behind the choice of repair pathway.
Previously, Shibata has shown that the NHEJ was the default choice for repairing DSBs, but that HRR is then selected if the re-joining does not occur properly. He has also shown a fundamental role of MRE11 nuclease in determining the type of repair that occurs at a DSB. Additionally, Shibata has shown the crucial role BRCA1 has in directing the repair of DSB towards the HRR pathway. In short, his work in the field is internationally recognised. 'These studies have contributed to the establishment of research basis for the recent discovery in the study of transcription-associated HRR,' observes Shibata.

Keywords: BREAK IN DOUBLE STRAND IN THE DNA; DNA REPAIR; HOMOLOGOUS RECOMBINATION REPAIR (HRR); NON-HOMOLOGOUS END-JOINING (NHEJ); REPAIR PATHWAY; REPAIRING DSBS; ROLE BRCA1 HAS IN DIRECTING THE REPAIR OF DSB TOWARDS THE HRR PATHWAY; SIGNALLING PATHWAYS

Document Type: Research Article

Publication date: March 1, 2019

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