Scheme: Newton Advanced Fellowship
Organisation: Francis Crick Institute
Dates: Mar 2015-Feb 2018
Summary: In eukaryotes, DNA replication occurs via the coordinated initiation at hundreds of replication origins. However, not all origins firing at the same time, the timing at which initiation takes places can vary widely between origins. The replication timing decision point is probably established in the G1 phase, but the molecular mechanisms for orchestrating DNA replication timing have remained elusive. We propose that replication factors, such as Cdc6/MCM2-7/Cdc45/GINS, might dictate the time of origin firing in G1 phase. In the current research, we utilizes the nuclear extracts from Saccharomyces cerevisiae which support the de novo DNA replication under physiological relevant conditions and devises single-molecule approaches to visualize the assembly or displacement of these replication factors on DNA in real-time during the origin firing. We expect to decipher the mechanisms of DNA replication timing. Meanwhile, our lab is also interested in applying single-molecule and single-cell methods to study the mechanisms which underlie DNA replication, DNA damage repair, nucleosome assembly, aging and cell-to-cell communication in the eukaryotic model organism, Saccharomyces cerevisiae.