The Blow Lab:

CR-UK Chromosome Replication Research Group

Some current research projects:

Origin licensing and its regulation

Dormant origins and the response to replicative stress

Proteomic analysis of chromatin-associated proteins during the cell cycle

Regulation of replication factories in normal and cancer cells

During S phase, two protein kinases - cyclin-dependent kinases (CDKs) and the Cdc7 kinase - act on licensed origins to initiate a pair of replication forks. This involves the recruitment to chromatin of a range of replication fork proteins, including Cdc45 and the GINS complex which activate Mcm2-7 as a DNA helicase to drive progression of the replication fork.

In order for cell division to produce two daughter cells that inherit a perfect copy of the genetic material originally present in the mother cell, two difficult tasks must be accomplished: the chromosomal DNA must first be precisely duplicated, with no errors, deletions or duplications, and then the two copies must be precisely segregated to the two daughter cells. The accuracy of these events is particularly crucial to multicellular organisms, where any changes to the genome could potentially give rise to cancers which threaten the life of the entire organism.

The replication licensing system plays a fundamental role in preventing sections of chromosomal DNA from replicating more than once in a single cell cycle. Origin licensing comprises the ordered chromatin loading of the Origin Recognition Complex (ORC), Cdc6, Cdt1 and finally the Mcm2-7 complex (the probable replicative helicase) onto origins of replication. Origin licensing can only occur during late mitosis and early G1. Once a licensed origin initiates in S phase, the Mcm2-7 complex travels ahead of the fork, unwinding the DNA to allow access by the replication machinery, thereby leaving behind an unlicensed replication origin.

To find out more about how we do research, please see our film ‘Sharing Science’