BRCA1 and BRCA2 in DNA damage and replication stress response: Insights into their functions, mechanisms, and implications for cancer treatment

Genomic stability is a cornerstone of cellular survival and proliferation. To counter the constant threat posed by endogenous and exogenous DNA-damaging agents, cells rely on a network of intricate mechanisms to safeguard DNA integrity and ensure accurate replication. Among these, the BRCA1 and BRCA2 tumor suppressor proteins play pivotal roles. While traditionally recognized for their involvement in homologous recombination repair and cell cycle checkpoints, emerging evidence highlights their essential functions in protecting stalled replication forks during replication stress. Mutations in BRCA1 or BRCA2 disrupt these critical functions, leading to compromised genome stability and an increased susceptibility to various cancers, particularly breast and ovarian cancers. This review provides a comprehensive analysis of the multifaceted roles of BRCA1 and BRCA2, focusing on their contributions to DNA damage responses and replication stress management. By elucidating the molecular pathways through which BRCA1 and BRCA2 operate, we aim to provide insights into their pivotal roles in maintaining genomic integrity and their implications for cancer treatment.