RFC4

RFC4
Identifiers
Aliases	RFC4 , A1, RFC37, replication factor C subunit 4
External IDs	OMIM: 102577; MGI: 2146571; HomoloGene: 6288; GeneCards: RFC4; OMA:RFC4 - orthologs
Gene location (Human) Chr. Chromosome 3 (human) [1] Band 3q27.3 Start 186,789,880 bp [1] End 186,807,058 bp [1]
Gene location (Mouse) Chr. Chromosome 16 (mouse) [2] Band 16|16 B1 Start 22,932,693 bp [2] End 22,946,487 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ventricular zone ganglionic eminence gonad rectum testicle cerebellar hemisphere bone marrow right hemisphere of cerebellum mucosa of transverse colon appendix Top expressed in medial ganglionic eminence maxillary prominence mandibular prominence otic placode Gonadal ridge abdominal wall otic vesicle fetal liver hematopoietic progenitor cell endocardial cushion Paneth cell More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding DNA binding single-stranded DNA helicase activity protein binding enzyme binding ATP binding DNA clamp loader activity Cellular component DNA replication factor C complex Ctf18 RFC-like complex nucleus nucleoplasm Elg1 RFC-like complex Biological process nucleotide-excision repair, DNA gap filling error-free translesion synthesis DNA strand elongation involved in DNA replication error-prone translesion synthesis DNA replication positive regulation of DNA-directed DNA polymerase activity translesion synthesis transcription-coupled nucleotide-excision repair nucleotide-excision repair, DNA incision nucleotide-excision repair, DNA incision, 5'-to lesion DNA repair telomere maintenance via semi-conservative replication DNA-dependent DNA replication regulation of signal transduction by p53 class mediator Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5984 106344 Ensembl ENSG00000163918 ENSMUSG00000022881 UniProt P35249 Q99J62 RefSeq (mRNA) NM_181573 NM_002916 NM_145480 RefSeq (protein) NP_002907 NP_853551 NP_663455 Location (UCSC) Chr 3: 186.79 – 186.81 Mb Chr 16: 22.93 – 22.95 Mb PubMed search [3] [4]
Wikidata
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Replication factor C subunit 4 is a protein that in humans is encoded by the RFC4 gene. ^{[5] [6]}

Function

The elongation of primed DNA templates by DNA polymerase delta and DNA polymerase epsilon requires the accessory proteins proliferating cell nuclear antigen (PCNA) and replication factor C (RFC). RFC, also named activator 1, is a protein complex consisting of five distinct subunits of 140, 40, 38, 37, and 36 kD. This gene encodes the 37 kD subunit. This subunit forms a core complex with the 36 and 40 kDa subunits. The core complex possesses DNA-dependent ATPase activity, which was found to be stimulated by PCNA in an in vitro system. Alternatively spliced transcript variants encoding the same protein have been reported. ^[6]

Radioresistance of esophageal squamous carcinoma cells is a critical factor leading to treatment failure and recurrence. ^[7] RFC4 expression is significantly upregulated in esophageal squamous carcinoma cell tissues and cells, particurly in cases that are radioresistant. ^[7] RFC4 plays a role in conferring radioresistance to esophageal squamous cell carcinoma by bolstering repair of DNA damage. ^[7] Thus RFC4 is a promising therapeutic target for combating radioresistance in esophageal squamous cell carcinoma. ^[7]

Interactions

RFC4 has been shown to interact with:

• BRD4, ^[8]
• CHTF18, ^[9]
• PCNA, ^{[10] [11]}
• RFC2, ^{[10] [12]}
• RFC3, ^{[13] [14]} and
• RFC5. ^{[10] [12] [13] [15]}

References

1. GRCh38: Ensembl release 89: ENSG00000163918 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000022881 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Okumura K, Nogami M, Taguchi H, Dean FB, Chen M, Pan ZQ, Hurwitz J, Shiratori A, Murakami Y, Ozawa K (Jan 1995). "Assignment of the 36.5-kDa (RFC5), 37-kDa (RFC4), 38-kDa (RFC3), and 40-kDa (RFC2) subunit genes of human replication factor C to chromosome bands 12q24.2-q24.3, 3q27, 13q12.3-q13, and 7q11.23". Genomics. 25 (1): 274–8. doi:10.1016/0888-7543(95)80135-9. PMID   7774928.
6. "Entrez Gene: RFC4 replication factor C (activator 1) 4, 37kDa".
7. Yang T, Fan Y, Bai G, Huang Y (February 2025). "RFC4 confers radioresistance of esophagus squamous cell carcinoma through regulating DNA damage response". Am J Physiol Cell Physiol. 328 (2): C367 –C380. doi:10.1152/ajpcell.00533.2024. PMID   39672175.
8. Maruyama T, Farina A, Dey A, Cheong J, Bermudez VP, Tamura T, Sciortino S, Shuman J, Hurwitz J, Ozato K (Sep 2002). "A Mammalian bromodomain protein, brd4, interacts with replication factor C and inhibits progression to S phase". Molecular and Cellular Biology. 22 (18): 6509–20. doi:10.1128/mcb.22.18.6509-6520.2002. PMC   135621 . PMID   12192049.
9. Bermudez VP, Maniwa Y, Tappin I, Ozato K, Yokomori K, Hurwitz J (Sep 2003). "The alternative Ctf18-Dcc1-Ctf8-replication factor C complex required for sister chromatid cohesion loads proliferating cell nuclear antigen onto DNA". Proceedings of the National Academy of Sciences of the United States of America. 100 (18): 10237–42. Bibcode:2003PNAS..10010237B. doi: 10.1073/pnas.1434308100 . PMC   193545 . PMID   12930902.
10. Cai J, Gibbs E, Uhlmann F, Phillips B, Yao N, O'Donnell M, Hurwitz J (Jul 1997). "A complex consisting of human replication factor C p40, p37, and p36 subunits is a DNA-dependent ATPase and an intermediate in the assembly of the holoenzyme". The Journal of Biological Chemistry. 272 (30): 18974–81. doi: 10.1074/jbc.272.30.18974 . PMID   9228079.
11. Ohta S, Shiomi Y, Sugimoto K, Obuse C, Tsurimoto T (Oct 2002). "A proteomics approach to identify proliferating cell nuclear antigen (PCNA)-binding proteins in human cell lysates. Identification of the human CHL12/RFCs2-5 complex as a novel PCNA-binding protein". The Journal of Biological Chemistry. 277 (43): 40362–7. doi: 10.1074/jbc.M206194200 . PMID   12171929.
12. Cai J, Yao N, Gibbs E, Finkelstein J, Phillips B, O'Donnell M, Hurwitz J (Sep 1998). "ATP hydrolysis catalyzed by human replication factor C requires participation of multiple subunits". Proceedings of the National Academy of Sciences of the United States of America. 95 (20): 11607–12. Bibcode:1998PNAS...9511607C. doi: 10.1073/pnas.95.20.11607 . PMC   21688 . PMID   9751713.
13. Ellison V, Stillman B (Mar 1998). "Reconstitution of recombinant human replication factor C (RFC) and identification of an RFC subcomplex possessing DNA-dependent ATPase activity". The Journal of Biological Chemistry. 273 (10): 5979–87. doi: 10.1074/jbc.273.10.5979 . PMID   9488738.
14. Uhlmann F, Cai J, Flores-Rozas H, Dean FB, Finkelstein J, O'Donnell M, Hurwitz J (Jun 1996). "In vitro reconstitution of human replication factor C from its five subunits". Proceedings of the National Academy of Sciences of the United States of America. 93 (13): 6521–6. Bibcode:1996PNAS...93.6521U. doi: 10.1073/pnas.93.13.6521 . PMC   39056 . PMID   8692848.
15. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID   16189514. S2CID   4427026.

Further reading

• Chen M, Pan ZQ, Hurwitz J (Jun 1992). "Studies of the cloned 37-kDa subunit of activator 1 (replication factor C) of HeLa cells". Proceedings of the National Academy of Sciences of the United States of America. 89 (12): 5211–5. Bibcode:1992PNAS...89.5211C. doi: 10.1073/pnas.89.12.5211 . PMC   49261 . PMID   1351677.
• Uhlmann F, Cai J, Flores-Rozas H, Dean FB, Finkelstein J, O'Donnell M, Hurwitz J (Jun 1996). "In vitro reconstitution of human replication factor C from its five subunits". Proceedings of the National Academy of Sciences of the United States of America. 93 (13): 6521–6. Bibcode:1996PNAS...93.6521U. doi: 10.1073/pnas.93.13.6521 . PMC   39056 . PMID   8692848.
• Cujec TP, Cho H, Maldonado E, Meyer J, Reinberg D, Peterlin BM (Apr 1997). "The human immunodeficiency virus transactivator Tat interacts with the RNA polymerase II holoenzyme". Molecular and Cellular Biology. 17 (4): 1817–23. doi:10.1128/MCB.17.4.1817. PMC   232028 . PMID   9121429.
• Cai J, Gibbs E, Uhlmann F, Phillips B, Yao N, O'Donnell M, Hurwitz J (Jul 1997). "A complex consisting of human replication factor C p40, p37, and p36 subunits is a DNA-dependent ATPase and an intermediate in the assembly of the holoenzyme". The Journal of Biological Chemistry. 272 (30): 18974–81. doi: 10.1074/jbc.272.30.18974 . PMID   9228079.
• Loor G, Zhang SJ, Zhang P, Toomey NL, Lee MY (Dec 1997). "Identification of DNA replication and cell cycle proteins that interact with PCNA". Nucleic Acids Research. 25 (24): 5041–6. doi:10.1093/nar/25.24.5041. PMC   147130 . PMID   9396813.
• Ellison V, Stillman B (Mar 1998). "Reconstitution of recombinant human replication factor C (RFC) and identification of an RFC subcomplex possessing DNA-dependent ATPase activity". The Journal of Biological Chemistry. 273 (10): 5979–87. doi: 10.1074/jbc.273.10.5979 . PMID   9488738.
• Zhang G, Gibbs E, Kelman Z, O'Donnell M, Hurwitz J (Mar 1999). "Studies on the interactions between human replication factor C and human proliferating cell nuclear antigen". Proceedings of the National Academy of Sciences of the United States of America. 96 (5): 1869–74. Bibcode:1999PNAS...96.1869Z. doi: 10.1073/pnas.96.5.1869 . PMC   26703 . PMID   10051561.
• Uchiumi F, Watanabe M, Tanuma S (May 1999). "Characterization of telomere-binding activity of replication factor C large subunit p140". Biochemical and Biophysical Research Communications. 258 (2): 482–9. doi:10.1006/bbrc.1999.0589. PMID   10329413.
• van der Kuip H, Carius B, Haque SJ, Williams BR, Huber C, Fischer T (Apr 1999). "The DNA-binding subunit p140 of replication factor C is upregulated in cycling cells and associates with G1 phase cell cycle regulatory proteins". Journal of Molecular Medicine. 77 (4): 386–92. doi:10.1007/s001090050365. PMID   10353443. S2CID   22183443.
• Chaib H, Cockrell EK, Rubin MA, Macoska JA (2001). "Profiling and verification of gene expression patterns in normal and malignant human prostate tissues by cDNA microarray analysis". Neoplasia. 3 (1): 43–52. doi:10.1038/sj.neo.7900126. PMC   1505021 . PMID   11326315.
• Naiki T, Kondo T, Nakada D, Matsumoto K, Sugimoto K (Sep 2001). "Chl12 (Ctf18) forms a novel replication factor C-related complex and functions redundantly with Rad24 in the DNA replication checkpoint pathway". Molecular and Cellular Biology. 21 (17): 5838–45. doi:10.1128/MCB.21.17.5838-5845.2001. PMC   87303 . PMID   11486023.
• Lindsey-Boltz LA, Bermudez VP, Hurwitz J, Sancar A (Sep 2001). "Purification and characterization of human DNA damage checkpoint Rad complexes". Proceedings of the National Academy of Sciences of the United States of America. 98 (20): 11236–41. Bibcode:2001PNAS...9811236L. doi: 10.1073/pnas.201373498 . PMC   58713 . PMID   11572977.
• Griffith JD, Lindsey-Boltz LA, Sancar A (May 2002). "Structures of the human Rad17-replication factor C and checkpoint Rad 9-1-1 complexes visualized by glycerol spray/low voltage microscopy". The Journal of Biological Chemistry. 277 (18): 15233–6. doi: 10.1074/jbc.C200129200 . PMID   11907025.
• Anderson LA, Perkins ND (Aug 2002). "The large subunit of replication factor C interacts with the histone deacetylase, HDAC1". The Journal of Biological Chemistry. 277 (33): 29550–4. doi: 10.1074/jbc.M200513200 . PMID   12045192.
• Ohta S, Shiomi Y, Sugimoto K, Obuse C, Tsurimoto T (Oct 2002). "A proteomics approach to identify proliferating cell nuclear antigen (PCNA)-binding proteins in human cell lysates. Identification of the human CHL12/RFCs2-5 complex as a novel PCNA-binding protein". The Journal of Biological Chemistry. 277 (43): 40362–7. doi: 10.1074/jbc.M206194200 . PMID   12171929.
• Maruyama T, Farina A, Dey A, Cheong J, Bermudez VP, Tamura T, Sciortino S, Shuman J, Hurwitz J, Ozato K (Sep 2002). "A Mammalian bromodomain protein, brd4, interacts with replication factor C and inhibits progression to S phase". Molecular and Cellular Biology. 22 (18): 6509–20. doi:10.1128/MCB.22.18.6509-6520.2002. PMC   135621 . PMID   12192049.
• Anderson LA, Perkins ND (Jan 2003). "Regulation of RelA (p65) function by the large subunit of replication factor C". Molecular and Cellular Biology. 23 (2): 721–32. doi:10.1128/MCB.23.2.721-732.2003. PMC   151544 . PMID   12509469.
• Nagata T, Takahashi Y, Ishii Y, Asai S, Sugahara M, Nishida Y, Murata A, Chin M, Schichino H, Koshinaga T, Fukuzawa M, Mugishima H (Jun 2003). "Profiling of genes differentially expressed between fetal liver and postnatal liver using high-density oligonucleotide DNA array". International Journal of Molecular Medicine. 11 (6): 713–21. doi:10.3892/ijmm.11.6.713. PMID   12736711.