Research Summary

The role of BRCA2 and CDKN1A Interacting Protein (BCCIP) in replication stress response and DNA repair

Detailed understanding of the molecular mechanisms required for maintaining normal cell functions and the identification of key molecules whose alterations result in cancer development are crucial for early detection and prevention strategies of cancer.

Replication stress is a primary cause of genomic instability leading to oncogenic transformation. Since non-cancerous cells employ a combination of robust DNA repair pathways and mechanisms to repair replication induced DNA lesions, replication stress is a common feature among cancer and precancerous cells but not observed in non-cancerous cells. Exacerbating this property of cancer cells offers avenues for therapeutic intervention/s. Many components of Homologous-recombination (HR) mediated DNA repair, such as BRCA2 and RAD51 are involved in response to replication-stress where their functions are mechanistically different from their roles during HR-dependent DNA repair. The roles of many other repair proteins during replication stress response remain poorly understood. It is therefore, imperative to understand the mechanistic details of the processes that prevent replication stress. My research embarks upon investigating the role of a novel cancer associated gene named BRCA2 and CDKN1A Interacting Protein (BCCIP), specifically, the characterization of its functions in prevention of replication stress. This knowledge will be etiologically important for BCCIP deficient cancers.

Figure Legend: Model for HR independent role for BCCIP during DNA replication. BCCIP is required for recruiting BRCA2 which stabilizes the RAD51 filaments on stalled replication forks.
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