Two members of Cytosystems scientific board – Professor Ron Laskey and Dr Nicholas Coleman – co-authored a scientific paper on “Control of DNA replication and its potential clinical exploitation”, published in February 2005 by Nature Reviews at www.nature.com/reviews/cancer

You can view a copy of this paper in pdf format here.

Relevant excerpts:

“Multiple conserved mechanisms limit DNA replication to once per cell cycle. One vital level of control focuses on the loading of the heterohexameric ring of minichromosome maintenance proteins (MCMs) onto chromatin in the hierarchical assembly of the pre-replication complex at origins of replication. An essential role in proliferation for MCMs and their regulators makes them potentially important biomarkers for routine clinical use in cancer detection and prognosis.”

“Most cells in the human body are not cycling and exist in a state of quiescence (the G0 phase). A minority of actively cycling cells are located at specific sites in tissues such as epithelia (for example, in the cervix, colon and skin) and bone marrow. Exogenous growth factors stimulate cell-cycle entry from G0 into the first gap phase (G1). During late G1, cells are committed to DNA replication (which occurs in S phase), which is followed by a second gap phase (G2) and segregation of the replicated chromatin between the two daughter cells in mitosis (M).”

“The control of DNA replication is a rapidly advancing research field that is providing multiple opportunities for translational applications. The replication licensing proteins have emerged as important biomarkers in cancer pathology, with the potential to improve diagnosis, prognosis and assessment of treatment response for a range of common tumour types. These proteins also provide attractive drug targets, and the design of new anti-tumour therapies to target positive regulators of DNA replication, such as Pre-RC proteins, or to mimic the replication inhibitory function of geminin is a rich area for future exploitation.”