Replication Factor C
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The replication factor C, or RFC, is a five-subunit
protein complex A protein complex or multiprotein complex is a group of two or more associated polypeptide chains. Protein complexes are distinct from multienzyme complexes, in which multiple catalytic domains are found in a single polypeptide chain. Protein c ...
that is required for
DNA replication 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 inheritanc ...
. The subunits of this
heteropentamer A pentamer is an entity composed of five sub-units. In chemistry, it applies to molecules made of five monomers. In biochemistry, it applies to macromolecules, in particular to pentameric proteins, made of five proteic sub-units. In microbiolog ...
are named
Rfc1 Replication factor C subunit 1 is a protein that in humans is encoded by the ''RFC1'' gene. Function The protein encoded by this gene is the large subunit of replication factor C, which is a five subunit DNA polymerase accessory protein. Replic ...
,
Rfc2 Replication factor C subunit 2 is a protein that in humans is encoded by the ''RFC2'' gene. Function The elongation of primed DNA templates by DNA polymerase delta and epsilon requires the action of the accessory proteins, proliferating cell ...
,
Rfc3 Replication factor C subunit 3 is a protein that in humans is encoded by the ''RFC3'' gene. Function The elongation of primed DNA templates by DNA polymerase delta and DNA polymerase epsilon requires the accessory proteins proliferating cell ...
,
Rfc4 Replication factor C subunit 4 is a protein that in humans is encoded by the ''RFC4'' gene. Function The elongation of primed DNA templates by DNA polymerase delta and DNA polymerase epsilon requires the accessory proteins proliferating cell ...
, and
Rfc5 Replication factor C subunit 5 is a protein that in humans is encoded by the ''RFC5'' gene. Function The elongation of primed DNA templates by DNA polymerase delta and DNA polymerase epsilon requires the accessory proteins proliferating cell ...
in ''
Saccharomyces cerevisiae ''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been o ...
''. RFC is used in eukaryotic replication as a clamp loader, similar to the γ Complex in ''
Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
''. Its role as a clamp loader involves catalyzing the loading of
PCNA 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, wh ...
onto DNA. It binds to the 3' end of the DNA and uses ATP to open the ring of PCNA so that it can encircle the DNA. ATP hydrolysis causes the release of RFC, with concomitant clamp loading onto DNA. For DNA polymerase, RFC serves as primer identification. RFC plays an important role in the proliferation, invasion, and progression of various malignant tumors. RFC acts as a tumor suppressor gene.


RFC sub-units

The 5 subunits of replication factor C are 1.RFC1 40KDa 2.RFC2 0KDa 3.RFC3 8KDa 4.RFC4 7KDaref name=":0"> 5.RFC5 6KDa Eukaryotes, yeast, mice, drosophila, calf thymus, humans, rice, and Arabidopsis all contain 5 subunits. There are genes such as 13q12.3-q13, 3q27, and p140 FC1 p40 FC2 p38 FC3 p37 FC4p36 FC5are located on human chromosomal segments. RFC Boxes -8are the amino acid sequences found in human replication factor C. RFC 1 is the largest RFC subunit, with 8RFC Boxes. Other RFC subunits also have 7 RFC boxes. RFC box 1 has a 90 amino acid-long region, while RFC box 2 is a highly conserved subunit. RFC box 3 includes a phosphate-binding loop. RFC box 5 is the second most conserved box. RFC Box 6 is different between the two subunits such as one large 6a and small 6b subunits.


Physiological functions of RFC in Humans

RFC is involved in the maintenance of telomeres, nuclear DNA replication, mismatch repair, and nucleotide excision repair. In the presence of ATP, RFC can load Proliferating cell nuclear antigen CNAand DNA polymerase to form DNA-RFC-PCNA-DNA polymerase, which elongates in the presence of deoxynucleotides NTPsvia the action of human single-stranded DNA-binding protein SSB RFC acts as a DNA checkpoint, initiating repairs such as excisions and mismatch repair. RFC1 has a binding region that interacts with PCNA, which has been linked to Hutchinson-Gilford progeria syndrome
GPS The Global Positioning System (GPS), originally Navstar GPS, is a Radionavigation-satellite service, satellite-based radionavigation system owned by the United States government and operated by the United States Space Force. It is one of t ...
RFC prevents cell death caused by histone H3K56. RFC2 can load PCNA into chromatin during DNA replication and it is also involved in DNA replication and repair, as well as cell cycle checkpoints.


RFC as a checkpoint

To minimize somatic genetic alterations, checkpoint mechanisms stimulate a cell cycle halt at precise locations when DNA and perhaps other cellular constitutes are destroyed and sustain the arrested state till the signals clearly show the healing process from the injury is obtained. RFC5 and RCF2 are also engaged in DNA damage checkpoints and DNA replication checkpoints. Replication factor C is an emergency backup factor for DNA polymerases. RFC2 gene product required for a cell cycle checkpoint. RFC is a heteropentamer in budding yeast, it is encoded either by RFC1 and RFC2-5 genes. For polymerases δ and ε, RFC is a primer recognition factor. During chromosomal DNA replication, the RFC2 gene product meets the RFC1 and RFC5 specific genes, in addition to both DNA polymerases δ and ɛ. The rfc3+ gene is completely separated from fission yeast for DNA damage to regulate checkpoints. The checkpoint signal is also established by RFC3. To regulate the G2-M transition RFC proteins appear to be important in signal transmission to the checkpoint machinery.


References

DNA replication {{Protein-stub