FIG. 6.

Splicing-regulatory elements in BRCA1 exon 18 and creation of an ESS by the T6 mutant. WT exon 18 contains two weak ESEs (striped box) and two ESSs (black boxes), and its inclusion is largely dependent on 3′ and 5′ splice site definition. The G-to-T mutation at position +6 creates a strong silencer element at the 5′ end of the exon binding to hnRNPA1/A2 and DAZAP1 and may also disrupt a weak splicing enhancer. The ASF/SF2 ESE located in the middle of exon 18 stimulates BRCA1 exon 18 splicing only in the context of the T6 mutant.