About the Project
The four specific objectives are to:
1) Determine if the genomic breakpoints identified in ALL cells are bona fide recombinase targets.
2) Determine if the recombination by-product is present in ALL patient samples and test how long the by-product persists in these cells.
3) Test if the recombination by-product can really lead to disease progression using a model system based on ALL-progenitor cells.
4) Begin analysis of the recombination by-product/recombinase complex for longer term structural studies.
These studies will thus investigate a new mechanism by which a very frequent group of cancers is caused. In the longer term, it is hoped that these studies can help in the understanding of the risk factors, as well as the development of inhibitors, of these devastating diseases.
These studies will provide training in a broad range of modern techniques, including molecular biology, biochemistry, bioinformatics and preliminary structural biology analyses.
Please see also View Website. for a related project with a deadline of January 10th 2021.
Smith AL, Scott JNF and Boyes J (2019). The ESC: The Dangerous By-product of V(D)J Recombination. Front. Immunol. 10:1572. doi: 10.3389/fimmu.2019.01572
Thwaites DT, Carter C, Lawless D, Savic S, Boyes JM. (2019) A novel RAG1 mutation reveals a critical in vivo role for HMGB1/2 during V(D)J recombination. Blood 133, 820-829. doi: 10.1182/blood-2018-07-866939.
Scott JN, Kupinski AP, Kirkham CM, Tuma R, Boyes J. (2014) TALE proteins bind to both active and inactive chromatin. Biochem J. 458:153-8. doi: 10.1042/BJ20131327.
Bevington, S., and Boyes, J., (2013) Transcription-coupled Eviction of histones H2A/H2B governs V(D)J recombination. EMBO J. 32:1381-92
Palacios, D., Summerbell, D., Rigby, P.W.J. and Boyes, J. (2010) Interplay between DNA Methylation and Transcription Factor Availability: Implications for Developmental Activation of the Mouse Myogenin Gene. Molecular and Cellular Biology. 30, 3805-3815.
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