Importance of E3 Ligases for Preserving Genome Integrity: Progress and Challenges

Maintenance of genome integrity is crucial for the survival of an organism. However, our genome is constantly being challenged by several processes that cause cellular stress, resulting in chromosomal instability and the onset of diseases like cancer. Therefore, cells have evolved many dedicated pathways to preserve genomic integrity. The cell cycle is one of the precisely regulated cellular pathways in which the entire genome is duplicated, and one complete copy of the genome is transferred to each daughter cell. Genome duplication is initiated at the G1 phase, while complete duplication occurs at the S phase. Then, the duplicated genome is equally divided into progeny cells through mitosis. Thus, any deregulation of G1, S, and mitotic phases contributes to genome instability. In this review, we have highlighted the importance of ubiquitin signaling, especially E3 ligases, in maintaining genome integrity during replication and mitosis, as it controls the activation and inactivation of cell cycle regulator proteins.