TOPBP1 contains a transcriptional activation domain suppressed by two adjacent BRCT domains

Roni Hg Wright , Edward S Dornan , Mary M Donaldson , Iain M Morgan (1)

1 Institute of Comparative Medicine

TopBP1 has eight BRCT [BRCA1 carboxyl terminus] domains and is involved in initiating DNA replication and DNA damage checkpoint signalling and repair. Several BRCT domain containing proteins involved in mediating DNA repair have transcriptional regulatory domains, and as demonstrated for BRCA1 these regulatory domains are important in mediating the functions of these proteins. These transcriptional regulatory processes involve modification of chromatin and recent evidence has clearly demonstrated that the ability to modify chromatin plays an important role in regulating DNA damage signalling and repair. Here we report the identification of a TopBP1 transcriptional activation domain rich in hydrophobic residues interspersed with acidic amino acids, typical of previously identified transcriptional activation domains. This activator is silenced by two adjacent repressor domains encoded by BRCT2 and BRCT5 and experiments suggest that these repressors actively recruit repressor complexes. Both the activator and BRCT2 repressor domains function in yeast. This report identifies several chromatin modification domains encoded by TopBP1 and the implications of these findings are discussed in the context of the DNA damage response and the understanding of TopBP1 function.

Mots clés: Life Sciences

Roni Hg Wright, Edward S Dornan, Mary M Donaldson, Iain M Morgan. TOPBP1 contains a transcriptional activation domain suppressed by two adjacent BRCT domains. Biochemical Journal, 2006, 400 (3), pp.573-582. ⟨10.1042/BJ20060831⟩. ⟨hal-00478610⟩