The role of the BRCA1 tumour suppressor gene : from biochemistry to function

BRCA1 is an important tumour suppressor gene involved in hereditary breast and ovarian cancer. Since 1994 much research has focussed on what the normal functions of this gene are at the molecular, cellular and organismal level. BCRA1 has been implicated in a number of different cellular processes many of which act to maintain genome stability. However the molecular mechanisms by which BRCA1 acts have remained elusive. Recently BRCA1 has been shown to exhibit E3 ubiquitin ligase activity, a biochemical activity which may explain how the protein functions at the molecular level. The work described in this dissertation sets out to determine the relationship between the biochemical activities of BRCA1 (including ubiquitin ligase activity) and its most well defined functions at the cellular level. The chief conclusion from this work is that ubiquitin ligase activity is not required for mediating some of BRCA1’simportant functions. Instead the BRCT domains and the formation of a complex with another protein, BARD1, are essential for function.EThOS - Electronic Theses Online ServiceGBUnited Kingdo