RFC4 explained

Replication factor C subunit 4 is a protein that in humans is encoded by the RFC4 gene.^{[1] [2]}

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.

Interactions

RFC4 has been shown to interact with:

• BRD4,^[3]
• CHTF18,^[4]
• PCNA,^[5]
• RFC2,^{[6] [7]}
• RFC3,^{[8] [9]} and
• RFC5.^{[6] [7] [8] [10]}

Further reading

• Chen M, Pan ZQ, Hurwitz J . 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 . Jun 1992 . 1351677 . 49261 . 10.1073/pnas.89.12.5211 . 1992PNAS...89.5211C . free .
• Uhlmann F, Cai J, Flores-Rozas H, Dean FB, Finkelstein J, O'Donnell M, Hurwitz J . 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 . Jun 1996 . 8692848 . 39056 . 10.1073/pnas.93.13.6521 . 1996PNAS...93.6521U . free .
• Cujec TP, Cho H, Maldonado E, Meyer J, Reinberg D, Peterlin BM . The human immunodeficiency virus transactivator Tat interacts with the RNA polymerase II holoenzyme . Molecular and Cellular Biology . 17 . 4 . 1817–23 . Apr 1997 . 9121429 . 232028 . 10.1128/MCB.17.4.1817.
• Cai J, Gibbs E, Uhlmann F, Phillips B, Yao N, O'Donnell M, Hurwitz J . 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 . Jul 1997 . 9228079 . 10.1074/jbc.272.30.18974 . free .
• Loor G, Zhang SJ, Zhang P, Toomey NL, Lee MY . Identification of DNA replication and cell cycle proteins that interact with PCNA . Nucleic Acids Research . 25 . 24 . 5041–6 . Dec 1997 . 9396813 . 147130 . 10.1093/nar/25.24.5041 .
• Ellison V, Stillman B . 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 . Mar 1998 . 9488738 . 10.1074/jbc.273.10.5979 . free .
• Zhang G, Gibbs E, Kelman Z, O'Donnell M, Hurwitz J . 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 . Mar 1999 . 10051561 . 26703 . 10.1073/pnas.96.5.1869 . 1999PNAS...96.1869Z . free .
• Uchiumi F, Watanabe M, Tanuma S . Characterization of telomere-binding activity of replication factor C large subunit p140 . Biochemical and Biophysical Research Communications . 258 . 2 . 482–9 . May 1999 . 10329413 . 10.1006/bbrc.1999.0589 .
• van der Kuip H, Carius B, Haque SJ, Williams BR, Huber C, Fischer T . 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 . Apr 1999 . 10353443 . 10.1007/s001090050365 . 22183443 .
• Chaib H, Cockrell EK, Rubin MA, Macoska JA . Profiling and verification of gene expression patterns in normal and malignant human prostate tissues by cDNA microarray analysis . Neoplasia . 3 . 1 . 43–52 . 2001 . 11326315 . 1505021 . 10.1038/sj.neo.7900126.
• Naiki T, Kondo T, Nakada D, Matsumoto K, Sugimoto K . 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 . Sep 2001 . 11486023 . 87303 . 10.1128/MCB.21.17.5838-5845.2001 .
• Lindsey-Boltz LA, Bermudez VP, Hurwitz J, Sancar A . 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 . Sep 2001 . 11572977 . 58713 . 10.1073/pnas.201373498 . 2001PNAS...9811236L . free .
• Griffith JD, Lindsey-Boltz LA, Sancar A . 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 . May 2002 . 11907025 . 10.1074/jbc.C200129200 . free .
• Anderson LA, Perkins ND . The large subunit of replication factor C interacts with the histone deacetylase, HDAC1 . The Journal of Biological Chemistry . 277 . 33 . 29550–4 . Aug 2002 . 12045192 . 10.1074/jbc.M200513200 . free .
• Ohta S, Shiomi Y, Sugimoto K, Obuse C, Tsurimoto T . 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 . Oct 2002 . 12171929 . 10.1074/jbc.M206194200 . free .
• Maruyama T, Farina A, Dey A, Cheong J, Bermudez VP, Tamura T, Sciortino S, Shuman J, Hurwitz J, Ozato K . A Mammalian bromodomain protein, brd4, interacts with replication factor C and inhibits progression to S phase . Molecular and Cellular Biology . 22 . 18 . 6509–20 . Sep 2002 . 12192049 . 135621 . 10.1128/MCB.22.18.6509-6520.2002 .
• Anderson LA, Perkins ND . Regulation of RelA (p65) function by the large subunit of replication factor C . Molecular and Cellular Biology . 23 . 2 . 721–32 . Jan 2003 . 12509469 . 151544 . 10.1128/MCB.23.2.721-732.2003 .
• Nagata T, Takahashi Y, Ishii Y, Asai S, Sugahara M, Nishida Y, Murata A, Chin M, Schichino H, Koshinaga T, Fukuzawa M, Mugishima H . 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 . Jun 2003 . 12736711 . 10.3892/ijmm.11.6.713 .

Notes and References

1. Okumura K, Nogami M, Taguchi H, Dean FB, Chen M, Pan ZQ, Hurwitz J, Shiratori A, Murakami Y, Ozawa K . 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 . Jan 1995 . 7774928 . 10.1016/0888-7543(95)80135-9 .
2. Web site: Entrez Gene: RFC4 replication factor C (activator 1) 4, 37kDa.
3. Maruyama T, Farina A, Dey A, Cheong J, Bermudez VP, Tamura T, Sciortino S, Shuman J, Hurwitz J, Ozato K . A Mammalian bromodomain protein, brd4, interacts with replication factor C and inhibits progression to S phase . Molecular and Cellular Biology . 22 . 18 . 6509–20 . Sep 2002 . 12192049 . 135621 . 10.1128/mcb.22.18.6509-6520.2002.
4. Bermudez VP, Maniwa Y, Tappin I, Ozato K, Yokomori K, Hurwitz J . 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 . Sep 2003 . 12930902 . 193545 . 10.1073/pnas.1434308100 . 2003PNAS..10010237B . free .
5. Ohta S, Shiomi Y, Sugimoto K, Obuse C, Tsurimoto T . 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 . Oct 2002 . 12171929 . 10.1074/jbc.M206194200 . free .
6. Cai J, Gibbs E, Uhlmann F, Phillips B, Yao N, O'Donnell M, Hurwitz J . 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 . Jul 1997 . 9228079 . 10.1074/jbc.272.30.18974. free .
7. Cai J, Yao N, Gibbs E, Finkelstein J, Phillips B, O'Donnell M, Hurwitz J . 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 . Sep 1998 . 9751713 . 21688 . 10.1073/pnas.95.20.11607. 1998PNAS...9511607C . free .
8. Ellison V, Stillman B . 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 . Mar 1998 . 9488738 . 10.1074/jbc.273.10.5979. free .
9. Uhlmann F, Cai J, Flores-Rozas H, Dean FB, Finkelstein J, O'Donnell M, Hurwitz J . 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 . Jun 1996 . 8692848 . 39056 . 10.1073/pnas.93.13.6521. 1996PNAS...93.6521U . free .
10. 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 . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . Oct 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .