Genome surveillance complex

BRCA1 is a component in a multi-subunit protein complex that includes DNA damage repair proteins. This complex includes other subunits of the RNA polymerase II holoenzyme and plays the role of genome surveillance during transcription.

The genome surveillance complex includes CDK7, MNAT1, and several of the excision repair cross-complementing (ERCC) proteins. It may also include members of the BRCA1-associated genome surveillance complex (BASC): MSH2-MSH6, MLH1, ATM, NBS1, MRE11, and BLM.

BRCA1

BRCA1 combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as BASC for BRCA1-associated genome surveillance complex. BRCA1 associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complex. BRCA1 thus plays a role in transcription, DNA repair of double-stranded breaks, and recombination.

MNAT1

MAT1 (for 'menage a trois-1') is involved in the assembly of the CAK complex. CAK is a multisubunit protein that includes CDK7, cyclin H (CCNH), and MAT1, which functions as a Cdk-activating kinase (CAK). It is an essential component of the transcription factor TFIIH, that is involved in transcription initiation and DNA repair.

TFIIH

The cyclin activating kinase-subcomplex (CDK7, MAT1, and cyclin H) is linked to the core complex of TFIIH via the XPD protein. Two of the subunits, ERCC2/XPD and ERCC3/XPB, have helicase and ATPase activities and help create the transcription bubble.

See also

• RNA polymerase II holoenzyme