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FUGE-Funksjonell genomforskn.i Norg

The Interactomics of DNA Repair

Tildelt: kr 5,3 mill.

The single most important factor for the correct functioning of genomes is that their coding information is maintained intact and transferred unperturbed to future generations. DNA repair is highly coordinated- and integrated with other fundamental cellul ar processes such as transcription, replication, cell-cycle control and apoptosis. Core elements of DNA repair has even been adapted as essential parts of the adaptive immune system in higher vertebrates. Thus, a fundamental understanding of the molecular mechanisms underlying genomic maintenance is central to our understanding of regulation of genomic function. This project focuses on the repair of misincorporated bases, AP-sites (missing bases) and well as bases subject to simple chemical modifications . Collectively such damages amounts to about 10 000 events in the genome of each human cell/day. The major pathway for repair of such lesions is base-excision repair (BER), anthough alternative pathways, such as direct repair of alkylation lesions by the human AlkB homologues contribute significantly. Although the core factors and enzymatic steps of these pathways have been identified, we still lack information on regulatory steps, accessory proteins, potential bottle-necks, regulation and significance of interactions, and function of posttranslational modifications. We also lack information on subnuclear localisation of the processes and recruitment of the various factors to the site of damage. Almost certainly several additional factors remain to be ide ntified. The strong background of our research group within mammalian DNA repair and genomic maintenance, extensive collaboration with leading groups both nationally and internationally, and in-house state-of the art technology within protein isolation, m ass spectrometry, molecular imaging, array technology and X-ray chrystallography indicate that we have the competence required to take on this important project within functional genomics.


FUGE-Funksjonell genomforskn.i Norg