Proliferating cell nuclear antigen: Difference between revisions

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[[File:Cryo-EM_structure_of_the_DNA-bound_PolD–PCNA_processive_complex.pdf|Cryo-EM structure of the DNA-bound PolD–PCNA processive complex|thumb]] '''Proliferating Cell Nuclear Antigen''' (PCNA) is a protein that plays a crucial role in [[DNA replication]] and [[DNA repair]] mechanisms within a cell. It acts as a processivity factor for [[DNA polymerase δ]] in eukaryotic cells, essentially encircling the [[DNA]] strand to increase the enzyme's ability to synthesize DNA efficiently. PCNA is a homotrimer, meaning it is composed of three identical subunits, which form a ring-shaped structure that can slide along the DNA strand.
{{DISPLAYTITLE:Proliferating Cell Nuclear Antigen}}


== Function ==
'''Proliferating Cell Nuclear Antigen''' (PCNA) is a protein that plays a crucial role in [[DNA replication]] and [[DNA repair]] mechanisms within a cell. It acts as a processivity factor for [[DNA polymerase δ]] in eukaryotic cells, essentially encircling the [[DNA]] strand to increase the enzyme's ability to synthesize DNA efficiently. PCNA is a homotrimer, meaning it is composed of three identical subunits, which form a ring-shaped structure that can slide along the DNA strand.
PCNA's primary function is to increase the [[DNA polymerase]]'s processivity, allowing for the rapid and efficient synthesis of DNA. This is crucial during the [[S phase]] of the [[cell cycle]], where DNA replication occurs. Besides its role in DNA synthesis, PCNA is involved in [[DNA repair]] processes, [[cell cycle regulation]], and [[chromatin assembly]]. It interacts with various proteins and serves as a platform for the assembly of protein complexes involved in these processes.


=== DNA Replication ===
==Structure==
During DNA replication, PCNA is loaded onto the DNA at the replication fork by the [[replication factor C]] (RFC) complex. Once loaded, it recruits DNA polymerase δ, enhancing its processivity. This interaction is vital for the synthesis of the lagging strand during replication.
[[File:Cryo-EM_structure_of_the_DNA-bound_PolD–PCNA_processive_complex.pdf|Cryo-EM structure of the DNA-bound PolD–PCNA processive complex|thumb|right]]
PCNA is a toroidal, or doughnut-shaped, protein complex. Each of its three subunits contributes to the formation of a central hole through which the DNA strand passes. This structure allows PCNA to act as a sliding clamp, maintaining its position on the DNA while allowing the polymerase to move along the strand during replication.


=== DNA Repair ===
==Function==
PCNA is also involved in several DNA repair pathways, including [[nucleotide excision repair]] (NER), [[base excision repair]] (BER), and [[mismatch repair]] (MMR). It recruits and interacts with various repair proteins at sites of DNA damage, facilitating the repair process.
PCNA is primarily known for its role in DNA replication, where it acts as a processivity factor for DNA polymerase δ. By encircling the DNA, PCNA increases the polymerase's ability to synthesize long stretches of DNA without dissociating. This is crucial for the rapid and accurate replication of the genome during cell division.


=== Cell Cycle Regulation ===
In addition to its role in replication, PCNA is also involved in DNA repair processes. It interacts with various proteins involved in [[nucleotide excision repair]], [[base excision repair]], and [[mismatch repair]], helping to coordinate the repair of damaged DNA.
PCNA plays a role in cell cycle regulation by interacting with proteins involved in cell cycle control. Its levels are tightly regulated throughout the cell cycle, peaking during the S phase.


== Clinical Significance ==
==Regulation==
Given its central role in DNA replication and repair, PCNA is a marker for cell proliferation. Elevated levels of PCNA are often observed in actively dividing cells, including cancer cells. As such, PCNA can be used as a prognostic marker in various cancers, indicating the aggressiveness of the tumor based on the level of cell proliferation.
The activity of PCNA is regulated by post-translational modifications, such as ubiquitination and sumoylation. These modifications can alter PCNA's interactions with other proteins and its role in DNA repair pathways. For example, ubiquitination of PCNA is involved in the [[translesion synthesis]] pathway, allowing the replication machinery to bypass DNA lesions.


== Structure ==
==Clinical Significance==
The PCNA protein is a homotrimer, with each monomer consisting of two similar domains that form a ring structure. This ring encircles the DNA, sliding along it during the replication process. The structure of PCNA allows it to interact with a wide range of proteins, facilitated by various PCNA-interacting protein (PIP) boxes and other interaction motifs.
PCNA is often used as a marker for cell proliferation in cancer research and diagnostics. Its expression levels correlate with the rate of cell division, making it a useful indicator of tumor growth and aggressiveness. Additionally, mutations or dysregulation of PCNA and its associated pathways can contribute to genomic instability and cancer development.


== Research and Applications ==
==Related Pages==
Research on PCNA continues to uncover its roles in DNA replication, repair, and cell cycle regulation. Understanding PCNA's interactions and functions at a molecular level can lead to the development of targeted therapies, especially in cancer treatment, where modulating DNA repair and cell proliferation pathways could be beneficial.
* [[DNA replication]]
* [[DNA repair]]
* [[DNA polymerase]]
* [[Cell cycle]]
* [[Cancer biology]]


[[Category:DNA replication]]
[[Category:DNA repair]]
[[Category:Proteins]]
[[Category:Proteins]]
[[Category:Cell biology]]
[[Category:Molecular biology]]
{{biology-stub}}
== Proliferating cell nuclear antigen ==
<gallery>
File:Cryo-EM_structure_of_the_DNA-bound_PolD–PCNA_processive_complex.pdf|Cryo-EM structure of the DNA-bound PolD–PCNA processive complex
</gallery>
<gallery>
File:Cryo-EM_structure_of_the_DNA-bound_PolD–PCNA_processive_complex.pdf|Cryo-EM structure of the DNA-bound PolD–PCNA processive complex
</gallery>

Latest revision as of 10:50, 23 March 2025


Proliferating Cell Nuclear Antigen (PCNA) is a protein that plays a crucial role in DNA replication and DNA repair mechanisms within a cell. It acts as a processivity factor for DNA polymerase δ in eukaryotic cells, essentially encircling the DNA strand to increase the enzyme's ability to synthesize DNA efficiently. PCNA is a homotrimer, meaning it is composed of three identical subunits, which form a ring-shaped structure that can slide along the DNA strand.

Structure[edit]

File:Cryo-EM structure of the DNA-bound PolD–PCNA processive complex.pdf PCNA is a toroidal, or doughnut-shaped, protein complex. Each of its three subunits contributes to the formation of a central hole through which the DNA strand passes. This structure allows PCNA to act as a sliding clamp, maintaining its position on the DNA while allowing the polymerase to move along the strand during replication.

Function[edit]

PCNA is primarily known for its role in DNA replication, where it acts as a processivity factor for DNA polymerase δ. By encircling the DNA, PCNA increases the polymerase's ability to synthesize long stretches of DNA without dissociating. This is crucial for the rapid and accurate replication of the genome during cell division.

In addition to its role in replication, PCNA is also involved in DNA repair processes. It interacts with various proteins involved in nucleotide excision repair, base excision repair, and mismatch repair, helping to coordinate the repair of damaged DNA.

Regulation[edit]

The activity of PCNA is regulated by post-translational modifications, such as ubiquitination and sumoylation. These modifications can alter PCNA's interactions with other proteins and its role in DNA repair pathways. For example, ubiquitination of PCNA is involved in the translesion synthesis pathway, allowing the replication machinery to bypass DNA lesions.

Clinical Significance[edit]

PCNA is often used as a marker for cell proliferation in cancer research and diagnostics. Its expression levels correlate with the rate of cell division, making it a useful indicator of tumor growth and aggressiveness. Additionally, mutations or dysregulation of PCNA and its associated pathways can contribute to genomic instability and cancer development.

Related Pages[edit]

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