In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part for biological inheritance. This is essential for cell division during growth and repair of damaged tissues, while it also ensures that each of the new cells receives its own copy of the DNA. The cell possesses the distinctive property of division, which makes replication of DNA essential.
A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA. These enzymes are essential for DNA replication and usually work in groups to create two identical DNA duplexes from a single original DNA duplex. During this process, DNA polymerase "reads" the existing DNA strands to create two new strands that match the existing ones. These enzymes catalyze the chemical reaction
S phase (Synthesis Phase) is the phase of the cell cycle in which DNA is replicated, occurring between G1 phase and G2 phase. Since accurate duplication of the genome is critical to successful cell division, the processes that occur during S-phase are tightly regulated and widely conserved.
The replisome is a complex molecular machine that carries out replication of DNA. The replisome first unwinds double stranded DNA into two single strands. For each of the resulting single strands, a new complementary sequence of DNA is synthesized. The Total result is formation of two new double stranded DNA sequences that are exact copies of the original double stranded DNA sequence.
Proliferating cell nuclear antigen (PCNA) is a DNA clamp that acts as a processivity factor for DNA polymerase δ in eukaryotic cells and is essential for replication. PCNA is a homotrimer and achieves its processivity by encircling the DNA, where it acts as a scaffold to recruit proteins involved in DNA replication, DNA repair, chromatin remodeling and epigenetics.
A DNA clamp, also known as a sliding clamp, is a protein complex that serves as a processivity-promoting factor in DNA replication. As a critical component of the DNA polymerase III holoenzyme, the clamp protein binds DNA polymerase and prevents this enzyme from dissociating from the template DNA strand. The clamp-polymerase protein–protein interactions are stronger and more specific than the direct interactions between the polymerase and the template DNA strand; because one of the rate-limiting steps in the DNA synthesis reaction is the association of the polymerase with the DNA template, the presence of the sliding clamp dramatically increases the number of nucleotides that the polymerase can add to the growing strand per association event. The presence of the DNA clamp can increase the rate of DNA synthesis up to 1,000-fold compared with a nonprocessive polymerase.
Eukaryotic DNA replication is a conserved mechanism that restricts DNA replication to once per cell cycle. Eukaryotic DNA replication of chromosomal DNA is central for the duplication of a cell and is necessary for the maintenance of the eukaryotic genome.
Checkpoint protein HUS1 is a protein that in humans is encoded by the HUS1 gene.
Replication factor C subunit 1 is a protein that in humans is encoded by the RFC1 gene.
Replication factor C subunit 4 is a protein that in humans is encoded by the RFC4 gene.
Replication factor C subunit 2 is a protein that in humans is encoded by the RFC2 gene.
The gene polymerase delta 1 (POLD1) encodes the large, POLD1/p125, catalytic subunit of the DNA polymerase delta (Polδ) complex. The Polδ enzyme is responsible for synthesizing the lagging strand of DNA, and has also been implicated in some activities at the leading strand. The POLD1/p125 subunit encodes both DNA polymerizing and exonuclease domains, which provide the protein an important second function in proofreading to ensure replication accuracy during DNA synthesis, and in a number of types of replication-linked DNA repair following DNA damage.
Replication factor C subunit 3 is a protein that in humans is encoded by the RFC3 gene.
Replication factor C subunit 5 is a protein that in humans is encoded by the RFC5 gene.
DNA polymerase delta subunit 3 is an enzyme that in humans is encoded by the POLD3 gene. It is a component of the DNA polymerase delta complex.
Chromosome transmission fidelity protein 18 homolog is a protein that in humans is encoded by the CHTF18 gene.
Sister chromatid cohesion refers to the process by which sister chromatids are paired and held together during certain phases of the cell cycle. Establishment of sister chromatid cohesion is the process by which chromatin-associated cohesin protein becomes competent to physically bind together the sister chromatids. In general, cohesion is established during S phase as DNA is replicated, and is lost when chromosomes segregate during mitosis and meiosis. Some studies have suggested that cohesion aids in aligning the kinetochores during mitosis by forcing the kinetochores to face opposite cell poles.
DNA polymerase delta(DNA Pol δ) is an enzyme complex found in eukaryotes that is involved in DNA replication and repair. The DNA polymerase delta complex consists of 4 subunits: POLD1, POLD2, POLD3, and POLD4. DNA Pol δ is an enzyme used for both leading and lagging strand synthesis. It exhibits increased processivity when interacting with the proliferating cell nuclear antigen (PCNA). As well, the multisubunit protein replication factor C, through its role as the clamp loader for PCNA is important for DNA Pol δ function.
DNA polymerase epsilon catalytic subunit is an enzyme that in humans is encoded by the POLE gene. It is the central catalytic subunit of DNA polymerase epsilon.
DNA polymerase epsilon is a member of the DNA polymerase family of enzymes found in eukaryotes. It is composed of the following four subunits: POLE, POLE2, POLE3, and POLE4. Recent evidence suggests that it plays a major role in leading strand DNA synthesis and nucleotide and base excision repair.
