Role of BRCA2 in DNA repair

Abstract

BRCA2 is a tumour suppressor gene that maintains genomic stability by affecting proper DNA double-strand break repair. Our recent investigations suggested the involvement of BRCA2 in O6-alkylguanine DNA alkyltransferase (AGT) mediated DNA repair. Ubiquitously expressed AGT is believed to directly repair alkyl DNA lesions. This study assesses the importance of BRAC2 in this seemingly single step repair process. Interaction between BRCA2 and AGT is recognised. It is shown that cellular BRCA2 binds alkylated AGT preferentially. The ability of GFP tagged full length AGT to rescue sensitivity to alkylating drug is established in an AGT null cell line allowing for future AGT trafficking studies. The N-terminus of BRCA2 harbouring a transcription activation domain is capable of AGT expression regulation. These findings reveal that BRCA2 provides multiple levels of control over AGT biology such information is of tremendous value in the clinical management of tumours overexpressing AGT.