Functional assessment of intrinsic disorder central domains of BRCA1

Abstract

The most studied function of BRCA1 is that of tumor suppression through its role in DNA repair and transcription regulation. Germline mutations discovered in a larger cohort of patients, abrogate BRCA1 interactions with reported cellular partners, and are responsible for breast and ovarian cancer. The different functional regions of BRCA1 interact with nearly 30 different cellular partners. Thus, it becomes clinically significant to understand the detailed protein-protein interactions associated with functional regions of BRCA1. Different overlapping central domains of BRCA1 have been characterized using in silico, in vitro and biophysical approaches. To our conclusions, it has been observed that central domains of BRCA1 are intrinsically disordered and has large hydrodynamic radius with random coil like structures.

Keywords:

• BRCA1 central domains
• intrinsic disorder
• protein-protein interactions

Acknowledgements

The authors would like to acknowledge Mahamaya Biswal, Neha Behare and Hafiza Mahadik for their help in cloning and purification. The authors would like to acknowledge the Mass Spectrometry, BTIS facility of TMC-ACTREC.

Additional information

Funding

Funding for this study was supported by DBT (BT/513/NE/TBP/2013), Seed in Air grant from TMC. MVH thanks DAE, for the award of Raja Ramanna fellowship.