Research Fellows Directory
Dr Xiaodong Zhang
Imperial College London
DNA contains the information required for cells to replicate and transcribe. However, DNA is exposed to toxic chemicals, UV and other harmful radiation and consequently tens of thousands of DNA bases are damaged in each human cell every day. This damaged DNA needs to be repaired promptly, because failure to do so can result in genetic mutations that can have detrimental effects including cell death and cancer development. Cells have therefore evolved sophisticated systems to sense, signal and repair this damage. These signalling cascades are primarily mediated by phosphoinositide 3-kinase-related protein kinases (PIKKs) ATM, ATR and DNA-PK. ATR (and its yeast orthologue Mec1) and its partner, ATR-interacting protein (ATRIP, Ddc2 in yeast), are recruited to stalled DNA replication forks and damaged DNA sites to activate various target proteins that orchestrate cell cycle arrest and DNA damage repair. One of the most severe types of DNA damage is DNA double-strand break (DSB) as failure to repair it can cause apoptosis while mis-repair can result in mutations, chromosomal duplication, translocation or deletions. Homologous recombination (HR) is the most faithful repair mechanism as it restores the precise DNA sequence of the broken DNA ends by utilizing a sister chromatid as a template. In HR, the breast cancer susceptibility gene product, BRCA2 and its associated factor PALB2, assist RAD51 recombinase to initiate strand invasion and homologous recombination. In both yeast and human cells, the genomic DNA is tightly packaged into nucleosomes and chromatin in order to maintain genomic stability and rganisation. Understanding these fundamental processes is extremely important for our understanding of cancer development and the aging process, providing new avenues for future therapeutic development. We are currently characterizing the 3D structures of these important players in order to understand how they function.
Interests and expertise (Subject groups)