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damage foci and are thought to have a signalling role, (NAD)-dependent DNA ligase [11] have been determined. Review TRENDS in Biochemical Sciences Vol.29 No.11 November 2004mechanisms that enable mammalian cells to respond todamage response. Here we review the structure of BRCT repeats, their mechanisms of interacting with phosphorylated and non-phosphorylated protein targets, and the role of these interactions in key networks that regulate DNA repair. Discovery of the BRCT repeat module The BRCA1 protein, which is associated with hereditary breast and ovarian cancer, is intimately linked to The basic structure seems to be well conserved in all of these BRCT repeats, with the exception of the a2 helix, whose sequence is poorly conserved and is absent in the repeat of DNA ligase III. Although the C-terminal BRCT repeat of XRCC1 can exist as a well-folded isolated domain, most of the BRCT repeats that have been detected occur in multiples. Struc-tural studies of the BRCT repeats of BRCA1 have shown that the pair of repeats in this protein pack in a head-to-domains have a central role in coordinating the DNA cycle checkpoint proteins further suggests that these BRCA1 [7,8] (Figure 1a), 53BP1 [8,9] (Figure 1b), DNA ligase III [10] and an nicotinamide adenine dinucleotideJ.N. Mark Glover, R. Scott Williams and