BCCIP is known to associate with BRCA2 and RAD51 during HR-mediated DNA repair. It is recruited to stalled replication forks and prevents the degradation of nascent DNA strands by the MRE11 nuclease . This function is essential for protecting the integrity of the genome, especially under conditions of replication stress, which can lead to genomic instability and oncogenic transformation if not properly managed .
Replication stress occurs when the progression of replication forks is hampered, leading to the formation of DNA lesions such as double-strand breaks (DSBs). BCCIP plays a pivotal role in stabilizing these stalled replication forks and preventing their collapse. In the absence of BCCIP, there is an increase in replication fork stalling and subsequent DNA double-strand break formation . This highlights the importance of BCCIP in maintaining the stability of the genome during DNA replication.
Studies using mouse models have demonstrated the essential roles of BCCIP in embryonic development and chromosome stability. Conditional knockdown of BCCIP in mice leads to impaired cellular proliferation and increased apoptosis, resulting in embryonic lethality before day E11.5 . BCCIP-deficient mouse embryonic fibroblasts (MEFs) exhibit significant chromosomal structural alterations, including increased chromatid breaks and sister chromatid union (SCU), which can impair chromosome segregation during mitosis .
Given its critical role in DNA repair and genomic stability, BCCIP is a protein of interest in cancer research. Deficiencies in BCCIP function can lead to increased genomic instability, a hallmark of cancer development. Understanding the mechanisms by which BCCIP operates can provide insights into potential therapeutic targets for cancer treatment.