3.6.4.B8: clamp-loader complex
This is an abbreviated version!
For detailed information about clamp-loader complex, go to the full flat file.
Word Map on EC 3.6.4.B8
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3.6.4.B8
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chromatin
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slide
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sliding
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fork
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helicase
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polymerases
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orc1
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single-stranded
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mitosis
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rad9
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pre-replication
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pre-rcs
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schizosaccharomyces
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pombe
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s-phase
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license
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minichromosome
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prereplicative
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rpa
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encircle
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cdt1
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ring-shaped
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replisome
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heterochromatin
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firing
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hydroxyurea
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unwind
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telomeres
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primer-template
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okazaki
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translesion
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primase
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mating-type
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pcna-binding
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winged-helix
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rad3-related
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atr-mediated
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mcm3
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pcna-dependent
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geminin
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atr-dependent
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replicases
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chromatin-bound
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dnax
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atr-chk1
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lagging-strand
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template-primer
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fen1
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topbp1
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claspin
- 3.6.4.B8
- chromatin
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slide
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sliding
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fork
- helicase
- polymerases
- orc1
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single-stranded
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mitosis
- rad9
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pre-replication
-
pre-rcs
- schizosaccharomyces
- pombe
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s-phase
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license
-
minichromosome
-
prereplicative
- rpa
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encircle
- cdt1
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ring-shaped
- replisome
- heterochromatin
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firing
- hydroxyurea
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unwind
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telomeres
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primer-template
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okazaki
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translesion
- primase
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mating-type
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pcna-binding
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winged-helix
- rad3-related
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atr-mediated
- mcm3
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pcna-dependent
- geminin
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atr-dependent
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replicases
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chromatin-bound
- dnax
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atr-chk1
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lagging-strand
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template-primer
- fen1
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topbp1
- claspin
Reaction
Synonyms
9-1-1 loader, ATP-dependent clamp loader complex, ATPase, cell cycle checkpoint protein, clamp loader, clamp loader complex, CLC, CTF18-RFC, ELG1-RFC, gamma clamp loader, gamma clamp loader complex, MacRFC complex, ORC, origin recognition complex, PCNA unloader, primary PCNA loader, RAD17, replication factor C, RF-C/activator 1 homolog, RFC, RFC clamp loader complex, RFC complex, RFC1, secondary PCNA loader, SsoRFC-complex
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General Information
General Information on EC 3.6.4.B8 - clamp-loader complex
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evolution
malfunction
Q13415; Q13416; Q9UBD5; O43929; O43913; Q9Y5N6
ORC molecular defects are observed in Meier-Gorlin syndrome mutations
metabolism
physiological function
additional information
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most archaeal genomes also encode two RFC homologs, designated the RFC large (RFC-L) and small (RFC-S) subunits, that assemble to form a pentameric complex that contains one RFC-L and four RFC-S subunits
evolution
the clamp loader complex is a member of the AAA+ family of ATPases (adenosine 5'-triphosphatases)
evolution
Q13415; Q13416; Q9UBD5; O43929; O43913; Q9Y5N6
the enzyme complex belongs to the AAA+ ATPase family. The complex is composed of an ORC1/4/5 motor module lobe in an organization reminiscent of the DNA polymerase clamp loader complexes. The structure of HsORC reveals a remarkable similarity between two very different ATPases: the replication initiator ORC-CDC6 ATPase and the replication fork DNA polymerase clamp loader. Both ATPases function at different times during genome replication but load ring-shaped proteins onto double-stranded DNA so that the ring-shaped proteins become topologically linked to the DNA double helix. The ATPase motor module of HsORC is very reminiscent of the DNA polymerase clamp loader complexes such as replication factor C (RFC) in eukaryotes, the bacterial gamma-complex, and the T4 bacteriophage Gene44 clamp loader
evolution
O75943, P35251; P35250; P40938; P35249; P40937
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
evolution
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most archaeal genomes also encode two RFC homologs, designated the RFC large (RFC-L) and small (RFC-S) subunits, that assemble to form a pentameric complex that contains one RFC-L and four RFC-S subunits
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O75943, P35251; P35250; P40938; P35249; P40937
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
metabolism
O75943, P35251; P35250; P40938; P35249; P40937
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
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sliding clamps play central roles in a broad range of DNA replication and repair processes. The clamps form circular molecules that must be opened and resealed around DNA by the clamp loader complex to fulfil their function
physiological function
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proliferating cell nuclear antigen (PCNA) monomers assemble to form a ring-shaped clamp complex that encircles duplex DNA. PCNA binding to other proteins tethers them to the DNA providing contacts and interactions for many other enzymes essential for DNA metabolic processes. The PCNA clamp does not assemble autonomously but is loaded onto DNA by the replication factor C (RFC) clamp loader complex. RFC recognizes the 3' end of a single-strand/duplex DNA (primer-template) junction and uses the energy of ATP hydrolysis to assemble the PCNA ring around the primer. Primer extension by PolB is completely dependent on the presence of RFC plus either PCNA1 or PCNA2, and the rate of DNA synthesis increases when the PCNA1 or PCNA2 concentration is increased
physiological function
RFC is an ATPase. The RFC complex from Sulfolobus solfataricus physically interacts with DNA polymerase B1 (PolB1) and enhances both the polymerase and 3'-5' exonuclease activities of PolB1 in an ATP-independent manner. Stimulation of the PolB1 activity by RFC is independent of the ability of RFC to bind DNA but is consistent with the ability of RFC to facilitate DNA binding by PolB1 through protein-protein interaction. Sulfolobus RFC may play a role in recruiting DNA polymerase for efficient primer extension, in addition to clamp loading, during DNA replication. RFC is shown to interact with the PCNA1 and PCNA2 subunits through its small subunit RFCS and with PCNA3 through its large subunit RFCL
physiological function
O75943, P35251; P35250; P40938; P35249; P40937
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
physiological function
O75943, P35251; P35250; P40938; P35249; P40937
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
physiological function
O75943, P35251; P35250; P40938; P35249; P40937
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
physiological function
O75943, P35251; P35250; P40938; P35249; P40937
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
physiological function
P35251; P35250; P40938; P35249; P40937
sliding clamp proteins encircle duplex DNA and are involved in processive DNA replication and the DNA damage response. Clamp proteins are ring-shaped oligomers (dimers or trimers) and are loaded onto DNA by an ATP-dependent clamp loader complex that ruptures the interface between two adjacent subunits. The hydrophobic network is shared among clamp proteins and exhibits a key in a keyhole pattern where a bulky aromatic residue from one clamp subunit is anchored into a hydrophobic pocket of the opposing subunit. Bioinformatics and dynamic network analyses show that this oligomeric latch is conserved across DNA sliding clamps from all domains of life and dictates the dynamics of clamp opening and closing
physiological function
sliding clamps are actively loaded onto primed template DNA by ATP-dependent clamp loader complexes. The complex of chi and psi enzyme complex subunits plays an important role in the processivity of Okazaki fragment synthesis
physiological function
the beta-clamp protein and the gamma clamp loader complex are essential components of bacterial DNA replication machinery. The beta-clamp is a ring-shaped homodimer that encircles DNA and increases the efficiency of replication by providing a binding platform for DNA polymerases and other replication-related proteins. The beta-clamp is loaded onto DNA by the five-subunit gamma clamp loader complex in a multi-step ATP-dependent process. The initial steps of this process involve the cooperative binding of the beta-clamp by the five subunits of ATP-bound clamp loader, which induces or traps an open conformation of the clamp. The delta subunit of the Escherichia coli clamp loader, or even its 140 residue N-terminal domain (called mini-delta), alone can shift conformational equilibrium of the beta-clamp towards the open state
physiological function
the clamp loader utilizes ATP binding and hydrolysis to load the sliding clamp onto the DNA at the primer template junction
physiological function
Q13415; Q13416; Q9UBD5; O43929; O43913; Q9Y5N6
the first step in genome replication, the binding of the origin recognition complex (ORC) at origins of DNA replication, triggers a series of highly coordinated steps leading to the assembly of pre-replicative complexes (pre-RCs) in a process that involves CDC6 binding to ORC. ORC and CDC6 then function as an ATP-dependent assembler that first recruits a ring-shaped MCM2-7 hexamer with bound Cdt1 to DNA, and then loads a second MCM2-7 hexamer in a head-to-head orientation, whereby this double hexamer is topologically linked to double-stranded DNA. The enzyme complex loads ring-shaped proteins onto double-stranded DNA so that the ring-shaped proteins become topologically linked to the DNA double helix
physiological function
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RFC is an ATPase. The RFC complex from Sulfolobus solfataricus physically interacts with DNA polymerase B1 (PolB1) and enhances both the polymerase and 3'-5' exonuclease activities of PolB1 in an ATP-independent manner. Stimulation of the PolB1 activity by RFC is independent of the ability of RFC to bind DNA but is consistent with the ability of RFC to facilitate DNA binding by PolB1 through protein-protein interaction. Sulfolobus RFC may play a role in recruiting DNA polymerase for efficient primer extension, in addition to clamp loading, during DNA replication. RFC is shown to interact with the PCNA1 and PCNA2 subunits through its small subunit RFCS and with PCNA3 through its large subunit RFCL
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physiological function
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proliferating cell nuclear antigen (PCNA) monomers assemble to form a ring-shaped clamp complex that encircles duplex DNA. PCNA binding to other proteins tethers them to the DNA providing contacts and interactions for many other enzymes essential for DNA metabolic processes. The PCNA clamp does not assemble autonomously but is loaded onto DNA by the replication factor C (RFC) clamp loader complex. RFC recognizes the 3' end of a single-strand/duplex DNA (primer-template) junction and uses the energy of ATP hydrolysis to assemble the PCNA ring around the primer. Primer extension by PolB is completely dependent on the presence of RFC plus either PCNA1 or PCNA2, and the rate of DNA synthesis increases when the PCNA1 or PCNA2 concentration is increased
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Q13415; Q13416; Q9UBD5; O43929; O43913; Q9Y5N6
determination and analysis of the structure of human ORC (HsORC motor module) in a functionally active, ATP-hydrolysis ready state, providing insight into ATP-dependent protein loading as well as DNA and CDC6 binding, structure-function relationship, overview. In the context of the motor module, only the ORC1/4 interface is a functional ATPase. Binding of ORC2-ORC3 modulates the ATPase activity of the ORC motor
additional information
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determination and analysis of the structure of human ORC (HsORC motor module) in a functionally active, ATP-hydrolysis ready state, providing insight into ATP-dependent protein loading as well as DNA and CDC6 binding, structure-function relationship, overview. In the context of the motor module, only the ORC1/4 interface is a functional ATPase. Binding of ORC2-ORC3 modulates the ATPase activity of the ORC motor
additional information
Escherichia coli clamp loader complex is comprised of seven subunits, each of these has critical roles in the function of the clamp loader. Determination and analysis of the solution structure of the complete seven subunit clamp loader complex using small angle X-ray scattering, model of the dynamic nature of the clamp loader complex, overview
additional information
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Escherichia coli clamp loader complex is comprised of seven subunits, each of these has critical roles in the function of the clamp loader. Determination and analysis of the solution structure of the complete seven subunit clamp loader complex using small angle X-ray scattering, model of the dynamic nature of the clamp loader complex, overview
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
additional information
P35251; P35250; P40938; P35249; P40937
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
additional information
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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
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
additional information
P35251; P35250; P40938; P35249; P40937
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
additional information
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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
additional information
structure of Escherichia coli clamp loader complex CLC in complex with primed template DNA (PDB ID 3GLI). The chi and psi subunits serve to link the clamp loader complex and ssDNA binding protein SSB, with chi binding to SSB. Through its interaction with the CLC and SSB, the chi-psi complex plays an important role in the processivity of Okazaki fragment synthesis. Folds of chi and psi are similar to mononucleotide and dinucleotide binding proteins, respectively
additional information
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structure of Escherichia coli clamp loader complex CLC in complex with primed template DNA (PDB ID 3GLI). The chi and psi subunits serve to link the clamp loader complex and ssDNA binding protein SSB, with chi binding to SSB. Through its interaction with the CLC and SSB, the chi-psi complex plays an important role in the processivity of Okazaki fragment synthesis. Folds of chi and psi are similar to mononucleotide and dinucleotide binding proteins, respectively