GENOME STABILITY & CHECKPOINT CONTROL: Linkage between genome stability and checkpoint control

• Research unit: EU RFP
• Project number: 01.0528

Key words (English)

Education; Training; Scientific Research; Social Aspects

Alternative project number (English)

EU project number: HPRN-CT-2002-00240

Research programs (English)

EU-programme: 5. Frame Research Programme - 4.1.1 Research training networks

Short description (English)

See abstract

Abstract (English)

The preservation of genome stability is an essential process in every living organism. DNA can be damaged by a variety of agents and in a number of ways, often with deleterious consequences to cell survival. To prevent such consequences, DNA damage triggers a multitude of responses in eukaryotic cells, including DNA damage signalling and repair, and delay of cell cycle progression until repair is complete. This latter response is referred to as the 'DNA damage checkpoint'. If this checkpoint fails for any reason, genome instability can result. In higher eukaryotes, this can lead to cancer, accelerated ageing and/or certain neurodegenerative disease states. In this application, a set of complementary genetic and biochemical approaches are proposed for the study of the linkage between genome stability maintenance and checkpoint control. The nine laboratories in the proposed network will use biological systems that will allow the efficient integration of these complementary approaches.

The main objectives to be addressed are briefly summarized as follows:
- To understand the molecular function of DNA helicases involved in the preservation of genomic stability in yeast and humans. These helicases include S. cerevisiae Sgs 1 p, Srs2p, Dna2p, Mph1p, and the human XPB, XPD, BLM and WRN proteins;
- To establish how the activity of DNA repair and recombination proteins is controlled by checkpoint proteins. The achievement of these objectives will allow the network to define the functions and interactions of the different components of the DNA replication, repair and recombination machineries and to understand the regulatory circuits connecting these processes with checkpoint control. This information is a prerequisite to obtaining a complete insight into cellular growth control and how these controls are modified during tumorigenesis and other disease states.

References in databases (English)

Swiss Database: Euro-DB of the
State Secretariat for Education and Research
Hallwylstrasse 4
CH-3003 Berne, Switzerland
Tel. [phone]
Swiss Project-Number: 01.0528