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Literature summary for 3.6.4.B8 extracted from
- Functions of multiple clamp and clamp-loader complexes in eukaryotic DNA replication (2017), Adv. Exp. Med. Biol., 1042, 135-162 .
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | required | Homo sapiens |  |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + H2O | Homo sapiens | - |
ADP + phosphate | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | O75943 | - |
- |
| Homo sapiens | P35251 AND P35250 AND P40938 AND P35249 AND P40937 | subunits 1 to 5 | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + H2O | - |
Homo sapiens | ADP + phosphate | - |
? | |
| additional information | DNA loading substrate of CTF18-RFC is proliferating-cell-nuclear-antigen (PCNA) | Homo sapiens | ? | - |
- |
|
| additional information | DNA loading substrate of ELG1-RFC is proliferating-cell-nuclear-antigen (PCNA) | Homo sapiens | ? | - |
- |
|
| additional information | DNA loading substrate of Rad17 is 9-1-1 | Homo sapiens | ? | - |
- |
|
| additional information | schematic model of substrate proliferating-cell-nuclear-antigen (PCNA) loading by RFC: the homotrimeric ring of PCNA has a head-to-tail configuration of subunits. Substrate PCNA is a hub protein That connects DNA replication and peripheral chromosomal reactions. The ring has asymmetric side surfaces known as the N face and C face. PCNA protomer has two repetitive domains, 1 and 2 that are bridged by IDCL, which is located on the C face. In the presence of ATP, RFC attaches to the C face, opens one interface between the subunits, and binds to the 3' primer-template junction. Upon ATP hydrolysis, the structure of RFC changes to dissociate from PCNA and DNA, leaving a closed PCNA ring that is loaded on the duplex DNA with the C face directed to the 3' end of the primer. Poldelta then binds to the 3' primer end using the C face of PCNA as its docking surface and synthesizes lagging-strand DNA processively. After completion of the DNA elongation, FEN1 and DNA ligase 1 are tethered sequentially to ligate the lagging strands. The dynamic status of PCNA on dsDNA is determined by structural analyses, single-molecule imaging, and molecular-dynamics simulations. PCNA moves along dsDNA in a diffusive fashion in both directions. Most of the time, PCNA tracks rotationally the helical pitch of dsDNA by tilting with the DNA axis. This rotational motion of the tilted PCNA on DNA facilitates formation of a large number of electrostatic interactions between DNA backbone and the positively charged residues lining the PCNA inner surface, and it may provide a structure that captures a proper PCNA-binding partner | Homo sapiens | ? | - |
- |
|
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| 9-1-1 loader | - |
Homo sapiens |
| cell cycle checkpoint protein | - |
Homo sapiens |
| CTF18-RFC | - |
Homo sapiens |
| ELG1-RFC | - |
Homo sapiens |
| PCNA unloader | - |
Homo sapiens |
| primary PCNA loader | - |
Homo sapiens |
| RAD17 | - |
Homo sapiens |
| RF-C/activator 1 homolog | - |
Homo sapiens |
| RFC1 | - |
Homo sapiens |
| secondary PCNA loader | - |
Homo sapiens |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | three RFC1 paralogues - RAD17, CTF18 (chromosome transmission fidelity 18), and ELG1 (enhanced level of genome instability 1, in human also called ATAD5, ATPase family, AAA domain containing 5 or FRAG1, FGF receptor activating protein 1) - have been identified in eukaryotes. Furthermore, three proteins that share significant amino acid sequence similarities with PCNA (RAD9, RAD1, and HUS1) are necessary for the checkpoint-response pathway, along with RAD17-RFC | Homo sapiens |
| metabolism | Poldelta alone can only incorporate several nucleotides at the primer end, whereas in the presence of proliferating cell nuclear antigen (PCNA), it can produce DNA strands longer than 200-300 nucleotides. The PCNA-RFC-Poldelta system can efficiently fill DNA gaps from short patches to lagging-strand sizes | Homo sapiens |
| metabolism | Poldelta alone can only incorporate several nucleotides at the primer end, whereas in the presence of proliferating cell nuclear antigen (PCNA), it can produce DNA strands longer than 200-300 nucleotides. The PCNA-RFC-Poldelta system can efficiently fill DNA gaps from short patches to lagging-strand sizes. Physiological functions and dynamics of proliferating-cell-nuclear-antigen (PCNA), overview | Homo sapiens |
| additional information | mechanism of primary PCNA and 9-1-1 loading and unloading by RFC and homologues, secondary PCNA loading by CTF18-RFC, unloading by ELG1-RFC, detailed overview. DNA-sequence-specific PCNA loading occurs via interaction of RFC with a sequence-specific DNA-binding protein | Homo sapiens |
| additional information | mechanism of primary PCNA loading and unloading by RFC and of 9-1-1 by Rad17, secondary PCNA loading by CTF18-RFC, unloading by ELG1-RFC, detailed overview. DNA-sequence-specific PCNA loading occurs via interaction of RFC with a sequence-specific DNA-binding protein | Homo sapiens |
| physiological function | functions of multiple clamp and clamp-loader complexes in eukaryotic DNA replication, detailed overview. Eukaryotes have multiple paralogues of sliding clamp, PCNA and its loader, RFC. Another alternative loader complex, CTF18-RFC, has a role that is distinguishable from the role of the canonical loader, RFC. CTF18-RFC interacts with one of the replicative DNA polymerases, Polepsilon, and loads PCNA onto leading-strand DNA. In the progression of S phase, the alternative PCNA loader maintains appropriate amounts of PCNA on the replicating sister DNAs to ensure that specific enzymes are tethered at specific chromosomal locations | Homo sapiens |
| physiological function | functions of multiple clamp and clamp-loader complexes in eukaryotic DNA replication, detailed overview. Eukaryotes have multiple paralogues of sliding clamp, PCNA and its loader, RFC. Another alternative loader complex, ELG1-RFC, has a role that is distinguishable from the role of the canonical loader, RFC. ELG1-RFC unloads PCNA after ligation of lagging-strand DNA. In the progression of S phase, the alternative PCNA loader maintains appropriate amounts of PCNA on the replicating sister DNAs to ensure that specific enzymes are tethered at specific chromosomal locations | Homo sapiens |
| physiological function | functions of multiple clamp and clamp-loader complexes in eukaryotic DNA replication, detailed overview. Eukaryotes have multiple paralogues of sliding clamp, PCNA and its loader, RFC. CTF18-RFC interacts with one of the replicative DNA polymerases, Polapsilon, and loads PCNA onto leading-strand DNA, and ELG1-RFC unloads PCNA after ligation of lagging-strand DNA. In the progression of S phase, these alternative PCNA loaders maintain appropriate amounts of PCNA on the replicating sister DNAs to ensure that specific enzymes are tethered at specific chromosomal locations | Homo sapiens |
| physiological function | functions of multiple clamp and clamp-loader complexes in eukaryotic DNA replication, detailed overview. Eukaryotes have multiple paralogues of sliding clamp, PCNA and its loader, RFC. The proliferating cell nuclear antigen (PCNA) paralogues, RAD9, HUS1, and RAD1 form the heterotrimeric 9-1-1 ring that is similar to the PCNA homotrimeric ring, and the 9-1-1 clamp complex is loaded onto sites of DNA damage by its specific loader RAD17-RFC. This alternative clamp-loader system transmits DNA-damage signals in genomic DNA to the checkpoint-activation network and the DNA-repair apparatus. Human Rad17 lacks the DNA binding domain compared to human RFC1. It acts as a cell cycle checkpoint protein, RAD17-RFC performs loading of the 9-1-1 clamp onto DNA. 9-1-1 and RAD17-RFC are involved in ATR activation, but are not required for phosphorylation of CHK2, a mediator kinase of the ATM pathway for response to double-strand breaks. Physiological functions of protein 9-1-1 | Homo sapiens |
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