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Unlocking the secrets of PCNA: How does it coordinate DNA repair and replication?
During the cell cycle, the precise coordination of DNA replication and repair is crucial, and the core of this process is proliferating cell nuclear antigen (PCNA). As an important DNA clamp, PCNA not only supports DNA polymerase δ (Pol δ) in eukaryotic cells, but also plays an important role in various key biological processes, contributing to cell survival and maintenance of functions. Crucial.
The structure of PCNA is a homotrimer composed of three identical monomers, which allows it to wrap around DNA like a ring lock. This mechanism allows PCNA to serve as a scaffold to recruit many proteins involved in DNA replication, repair, chromatin remodeling, and epigenetics to sites of DNA replication.
The main function of PCNA is to improve the continuity of DNA polymerase during the replication process, which is crucial for accurate genome replication.
Expression of PCNA in DNA synthesis
PCNA was first discovered as an antigen, especially during the DNA synthesis stage of cells. When cells enter S phase, the expression of PCNA increases significantly. Research shows that PCNA maintains the stability of this process by binding to DNA polymerase delta, and this synthesis process is coordinated by replication factor C (RFC), allowing PCNA to clamp DNA firmly.
The role of PCNA in DNA repair
With the emergence of DNA damage, PCNA's functions are not limited to replication. It is also involved in the repair of DNA damage, especially in the post-replication repair (PRR) pathway. This pathway includes two major sub-pathways: trans-lesion synthesis and template switching. PCNA plays a decisive role in these processes.
The sequence and structural features of PCNA allow specific modifications, such as ubiquitination, to activate different DNA repair pathways.
Interaction between PCNA and other proteins
PCNA can interact with many proteins, and these interactions can affect the efficiency and selection of DNA replication and repair. For example, through different interaction sites, many proteins contain APIMs that exhibit repair functions under genotoxic stress, while proteins adsorbed through PIP boxes are mainly involved in the regular DNA replication process.
Clinical application and future prospects
Due to the importance of PCNA in tumor biology, its antibodies are used as diagnostic and prognostic indicators. The expression of PCNA can be used to evaluate the proliferation of different tumors. In addition, new research shows that specific targeting of PCNA can become a potential target in anti-cancer therapies. For example, in 2023, Urban Hope National Medical Center released research showing that a targeted chemotherapy called AOH1996 is expected to inhibit tumor growth without causing significant side effects.
These findings point to the potential of PCNA in tumor treatment and spur further research into it as a therapeutic target.
How can PCNA play a greater role in future cancer research and treatment?
