个人简介

B.Sc. (Bachelor of Science) Ph.D. (Doctor of Philosophy)

研究领域

Molecular Biology and Disease

One major question in cancer genetics is to what extent chromosomal instability is the beginning of tumorigenesis. RecQ helicases have been called caretakers of the genome and it is well documented that the loss of RecQ function leads to the breakdown in the maintenance of genome integrity and an elevated predisposition to cancer. We are investigating the function of RecQ at the molecular level using Saccharomyces cerevisiae as a model system. It is quite evident that mechanisms that preserve genome stability in yeast are indeed the same as those which go awry in many mammalian cancers. We are focusing on the relationship between Sgs1 and the MRX complex and determining if RecQ helicases preserve fragile site stability in slow replicating regions of the genome. We are also interested to understand the mechanism of checkpoint activation during S phase. In particular how Mec1-Ddc2 (human ATR-ATRIP) is recruited to stalled replication forks to stabilize components of the replisome. It is well understood that Mec1-Ddc2 activates Rad53 and that it is recruited to both DSBs and stalled replication forks. However, much of what is thought to happen at stalled replication forks has been implied from events at DSBs. In mammals the affinity of ATRIP for RPA suggests a model in which ATR-ATRIP is recruited to DSBs through interaction with RPA-bound single-stranded DNA (ssDNA). Currently, we are characterizing Mec1-Ddc2 localization to stalled replication forks and the signals/factors involved in its recruitment.

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Ball, L.G., Zhang, K., Cobb, J.A., Boone, C. and Xiao, W. (2009) The yeast Shu complex couples error-free post-replication repair to homologous recombination. Mol Microbiol 73, 89-102. Tittel-Elmer, M.V., Alabert, C., Pasero, P., and Cobb, J.A. (2009) The MRX complex stabilizes the replisome independently of the S phase checkpoint during replication stress. EMBO Journal 28,1142-56. Borde, V. and Cobb, J.A. (2008) Double functions for the Mre11 complex during DNA double-strand break repair and replication. Int J Biochem Cell Biol, 41, 1249-1253. Cobb, J.A. and van Attikum, H. (2009) Mapping genomic targets of DNA helicases by chromatin immunoprecipitation in Saccharomyces cerevisiae. Helicases: Methods in Molecular Biology, Humana Press- Chapter 8, 113-127. Cobb, J.A. and Lees-Miller, S.P. (2009) DNA double strand break: Not all foci are created equal.Cell Cycle, 9, 3. Ball, L.G., Zhang, K., Cobb, J.A., Boone, C. and Xiao, W. (2009) The yeast Shu complex couples error-free post-replication repair to homologous recombination. Mol Microbiol 73, 89-102. Tittel-Elmer, M.V., Alabert, C., Pasero, P., and Cobb, J.A. (2009) The MRX complex stabilizes the replisome independently of the S phase checkpoint during replication stress. EMBO Journal28,1142-56.