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Content archived on 2024-04-30

Characterisation of a new human dna mismatch recognition

Objective



Research objectives and content
The objective is to define the function of a novel human DNA mismatch recognition activity. The host laboratory has identified a heterodimeric (subunits of approximately 140kDa and llOkDa) human mismatch binding complex which appears not to be required for postreplicative mismatch repair. The llOkDa component is a member of the SMC protein family. This family also includes the S. pombe RAD 18 and E. coli RecN gene products which are involved in recombinational DNA repair and the rejoining of double-strand DNA breaks. Recently, a bovine SMC homolog has been shown to be associated with a complex that promotes DNA recombination-like activities in vitro. The size and properties of this activity resemble those of the human mismatch recognition complex.
Peptide sequence obtained by mass specrometry in the host institution identified expressed sequence tags (EST) for both proteins. The clones have been obtained and will be used to isolate full length cDNAs. In vitro protein expression systems, including the yeast two hybrid system, will be used to investigate the interactions between the two component proteins of the complex and with other cellular proteins. This approach will help define the role of this mismatch recognition complex in recombination and/or DNA repair.
Training content (objective, benefit and expected impact)
The host laboratory has extensive experience in biochemical approaches to DNA repair, and in particular DNA mismatch repair. The candidate will obtain biochemical expertise in protein characterization and will learn how to carry out biochemical assays for DNA mismatch repair related functions. The candidate's own experience of the yeast two-hybrid system will be an essential asset in investigating the protein:protein interactions of the new mismatch recognition activity.

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RGI - Research grants (individual fellowships)

Coordinator

Imperial Cancer Research Fund (ICRF)
EU contribution
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Address
Clare Hall Laboratories Blanche Lane South Mimms
EN6 3LD Potters Bar
United Kingdom

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Total cost

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Participants (1)

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