Replication factor C
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[1]The replication factor C, or RFC, is a five-subunit[2] protein complex that is required for DNA replication.
The subunits of this heteropentamer are named Rfc1, Rfc2, Rfc3, Rfc4, and Rfc5 in Saccharomyces cerevisiae. RFC is used in eukaryotic replication as a clamp loader, similar to the γ Complex in Escherichia coli. Its role as clamp loader involves catalysing the loading of PCNA 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 release of RFC, with concomitant clamp loading onto DNA. For DNA polymerase, RFC serves as primer identification. RFC plays an important role in proliferation, invasion, progression in various malignant tumors. RFC acts as tumor suppressor gene.
RFC sub units
The 5 subunits of replication factor C are
1.RFC1[140KDa]
2.RFC2[40KDa]
3.RFC3[38KDa]
4.RFC4[37KDa][3]
5.RFC5[36KDa]
Eukaryotes, yeast, mice, drosophila, calf thymus, humans, rice, and Arabidopsis all contains 5 subunits. There are genes such as such as 13q12.3-q13, 3q27, and p140 [RFC1], p40[RFC2], p38[RFC3], p37[RFC4],p36 [RFC5] are located on human chromosomal segments. RFC Boxes [1-8] are 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.[3]
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 [PCNA] and DNA polymerase to form DNA-RFC-PCNA-DNA polymerase, which elongates in the presence of deoxynucleotides [dNTPs] via the action of human single stranded DNA-binding protein [hSSB]. 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 [HGPS] . RFC prevents cell death caused by histone H3K56. RFC2 can load PCNA into chromatin during DNA replication and it also involved in DNA replication and repair, as well as cell cycle checkpoints.
References
- ^ Tang H, Hilton B, Musich PR, Fang DZ, Zou Y (April 2012). "Replication factor C1, the large subunit of replication factor C, is proteolytically truncated in Hutchinson-Gilford progeria syndrome". Aging Cell. 11 (2): 363–365. doi:10.1111/j.1474-9726.2011.00779.x. PMC 3306506. PMID 22168243.
- ^ Replication+Protein+C at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- ^ a b Li Y, Gan S, Ren L, Yuan L, Liu J, Wang W, et al. (2018). "Multifaceted regulation and functions of replication factor C family in human cancers". American Journal of Cancer Research. 8 (8): 1343–1355. PMC 6129478. PMID 30210909.
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