Proteins involved in DNA Replication. Click on protein
to expand description
And1/Ctf4
And 1 interacts with Mcm10 in S phase. Suggested to
have some role in loading pol alpha onto chromatin
together with Mcm10 and Cdc45 (1).
In S.Cerevisiae Ctf4 is usually associated with cohesion but has been seen in replication fork complex(2)
1. Zhu,W., Ukomadu,C., Jha,S., Senga,T., Dhar,S.K., Wohlschlegel,J.A., Nutt,L.K., Kornbluth,S. and Dutta,A. (2007) Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication. Genes Dev 21, 2288-2299.
2. Gambus,A., Jones,R.C., Sanchez-Diaz,A., Kanemaki,M., van Deursen,F., Edmondson,R.D. and Labib,K. (2006) GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks. Nat Cell Biol 8, 358-366.
In S.Cerevisiae Ctf4 is usually associated with cohesion but has been seen in replication fork complex(2)
1. Zhu,W., Ukomadu,C., Jha,S., Senga,T., Dhar,S.K., Wohlschlegel,J.A., Nutt,L.K., Kornbluth,S. and Dutta,A. (2007) Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication. Genes Dev 21, 2288-2299.
2. Gambus,A., Jones,R.C., Sanchez-Diaz,A., Kanemaki,M., van Deursen,F., Edmondson,R.D. and Labib,K. (2006) GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks. Nat Cell Biol 8, 358-366.
BRCA1
Component of E3 ubiquitin ligase involved in DNA
repair. Thought to stabilize replication forks on
DNA damage (1).
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BRCA2
Involved in DNA repair by homologous recombination.
Regulates Rad51 function. Possible role in
stabilizing stalled forks
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Cdc24
Required for elongation step of DNA replication.
Linked to DNA polymerase delta function and Okazaki
fragment processing. Only identified in S.
pombe?
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Cdc45
Required for initiation and elongation steps of DNA
replication. May be part of Mcm27 helicase complex.
Required after preRC step for loading of various proteins for initiation and elongation eg pol alpha
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Required after preRC step for loading of various proteins for initiation and elongation eg pol alpha
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Cdc6
Cdk
Cyclin-dependent protein kinase required for
initiation of replication and for other subsequent
steps .
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Cdt1
Ciz1
Colocalises with sites of newly synthesised
DNA (1).
Interacts with human ERH homologue (enhancer
rudimentary homology) and
recruits ERH to replication foci
(2)
1. Ainscough,J.F., Rahman,F.A., Sercombe,H., Sedo,A., Gerlach,B. and Coverley,D. (2007) C-terminal domains deliver the DNA replication factor Ciz1 to the nuclear matrix. J Cell Sci 120, 115-124.
2. Lukasik,A., Uniewicz,K.A., Kulis,M. and Kozlowski,P. (2008) Ciz1, a p21 cip1/Waf1-interacting zinc finger protein and DNA replication factor, is a novel molecular partner for human enhancer of rudimentary homolog. FEBS J 275, 332-340.
1. Ainscough,J.F., Rahman,F.A., Sercombe,H., Sedo,A., Gerlach,B. and Coverley,D. (2007) C-terminal domains deliver the DNA replication factor Ciz1 to the nuclear matrix. J Cell Sci 120, 115-124.
2. Lukasik,A., Uniewicz,K.A., Kulis,M. and Kozlowski,P. (2008) Ciz1, a p21 cip1/Waf1-interacting zinc finger protein and DNA replication factor, is a novel molecular partner for human enhancer of rudimentary homolog. FEBS J 275, 332-340.
Csm3/Swi3/Tipin
Component of Tof1(swi1/Tim)-Mrc1
(claspin)-Csm3(Swi3/Tipin) replication pausing
checkpoint complex
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Dia 2
F box protein linked to replication and chromosome
stability in S cerevisiae (1).
1. Swaminathan,S., Kile,A.C., MacDonald,E.M. and Koepp,D.M. (2007) Yra1 is required for S phase entry and affects Dia2 binding to replication origins. Mol Cell Biol 27, 4674-4684.
1. Swaminathan,S., Kile,A.C., MacDonald,E.M. and Koepp,D.M. (2007) Yra1 is required for S phase entry and affects Dia2 binding to replication origins. Mol Cell Biol 27, 4674-4684.
Dpb11/Cut5/Rad4/Mus101/TopBP1
Required for initiation of DNA replication. Also
suggested roles in repair.
These proteins are grouped as having functional equivalence however at the sequence level they have different numbers of BRCT domains and the C terminal half is different between yeast and higher eukaryotes.
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These proteins are grouped as having functional equivalence however at the sequence level they have different numbers of BRCT domains and the C terminal half is different between yeast and higher eukaryotes.
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DDK (Cdc7/Hsk1 plus Dbf4/Dfp1)
Protein kinase required for initiation of DNA
replication, probably via phosphorylation
of Mcm2-7.
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Dna2
DNA polymerase alpha
Hetero-tetrameric polymerase which has intrinsic
DNA primase activity. Required for initial DNA
synthesis of leading strand at origins and for
priming of Okazaki fragments on lagging strand.
Probably none of the DNA synthesised by this
polymerase remains in the completed DNA strands
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DNA polymerase delta
Replicative polymerase; synthesizes DNA at the
replication fork. May function on the lagging
strand. Requires PCNA for processive DNA synthesis.
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DNA polymerase epsilon
Replicative polymerase; synthesizes DNA at the
replication fork. May function on the leading
strand
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ETG1
In Arabidopsis suggested to interact MCM2-7 and to
act as fork stability factor. (1)
Homologues Drosophila (1) and human (2) but not in yeast.
1. Takahashi,N., Lammens,T., Boudolf,V., Maes,S., Yoshizumi,T., De Jaeger,G., Witters,E., Inze,D. and De Veylder,L. (2008) The DNA replication checkpoint aids survival of plants deficient in the novel replisome factor ETG1. EMBO J 27, 1840-1851.
2. Sakwe,A.M., Nguyen,T., Athanasopoulos,V., Shire,K. and Frappier,L. (2007) Identification and characterization of a novel component of the human minichromosome maintenance complex. Mol Cell Biol 27, 3044-3055.
Homologues Drosophila (1) and human (2) but not in yeast.
1. Takahashi,N., Lammens,T., Boudolf,V., Maes,S., Yoshizumi,T., De Jaeger,G., Witters,E., Inze,D. and De Veylder,L. (2008) The DNA replication checkpoint aids survival of plants deficient in the novel replisome factor ETG1. EMBO J 27, 1840-1851.
2. Sakwe,A.M., Nguyen,T., Athanasopoulos,V., Shire,K. and Frappier,L. (2007) Identification and characterization of a novel component of the human minichromosome maintenance complex. Mol Cell Biol 27, 3044-3055.
FACT
Histone chaperone (composed of Spt16 and Pob3)
which facilitates RNA polymerase transcription.
Also found at replication forks and associated with
replication proteins and may facilitate replication
through chromatin
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Fen1
Geminin
Binds to and inactivates Cdt1, thereby regulating
licensing/pre-RC formation. Only found in metazoa.
Also suggested to promote preRC formation by Cdt1 binding
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Also suggested to promote preRC formation by Cdt1 binding
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GINS
Tetrameric complex composed of Sld5, Psf1, Psf2,
Psf3
Associates with pre-replicative complex around the time of initiation and moves with replication forks during elongation step.
Required for elongation stage of DNA replication and maybe part of the Mcm helicase complex. (1) (2) (3) (4)
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Associates with pre-replicative complex around the time of initiation and moves with replication forks during elongation step.
Required for elongation stage of DNA replication and maybe part of the Mcm helicase complex. (1) (2) (3) (4)
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HBO1
Myst family acetylase.
• In humans suggested to interacts directly with orc and cdt1 and mcms. Suggested to be involved ( essential?) for mcm loading. Also binds to origins and is degraded after initiation. Increases cdt1 over replication effects. (1)
• Suggested that needs to be phosphorylated by plk for activity (2)
1. Miotto,B. and Struhl,K. (2008) HBO1 histone acetylase is a coactivator of the replication licensing factor Cdt1. Genes Dev 22, 2633-2638.
2. Wu,Z.Q. and Liu,X. (2008) Role for Plk1 phosphorylation of Hbo1 in regulation of replication licensing. Proc Natl Acad Sci U S A 105, 1919-1924.
• In humans suggested to interacts directly with orc and cdt1 and mcms. Suggested to be involved ( essential?) for mcm loading. Also binds to origins and is degraded after initiation. Increases cdt1 over replication effects. (1)
• Suggested that needs to be phosphorylated by plk for activity (2)
1. Miotto,B. and Struhl,K. (2008) HBO1 histone acetylase is a coactivator of the replication licensing factor Cdt1. Genes Dev 22, 2633-2638.
2. Wu,Z.Q. and Liu,X. (2008) Role for Plk1 phosphorylation of Hbo1 in regulation of replication licensing. Proc Natl Acad Sci U S A 105, 1919-1924.
Ku
Suggested to be involved in initiation in Hela
cells (1)
1. Rampakakis,E., Di Paola,D. and Zannis-Hadjopoulos,M. (2008) Ku is involved in cell growth, DNA replication and G1-S transition. J Cell Sci 121, 590-600.
1. Rampakakis,E., Di Paola,D. and Zannis-Hadjopoulos,M. (2008) Ku is involved in cell growth, DNA replication and G1-S transition. J Cell Sci 121, 590-600.
Ligase
Joins Okazaki fragments during DNA replication.
Ligase activity also needed for DNA repair and
recombination.
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Mcm2-7
Assembled onto chromatin at ORC to form
‘pre-replicative complex’. On replication
initiation, Mcm2-7 moves away from ORC with
replication fork. Probably provides helicase
activity at fork, possibly in conjunction with
other proteins such as GINS and Cdc45. Displaced
from chromatin during S phase, probably on
replication termination.
Hexameric complex composed of Mcm2, Mcm3, Mcm4, Mcm5, Mcm6 & Mcm7. Note not related to Mcm1 or Mcm10.
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Hexameric complex composed of Mcm2, Mcm3, Mcm4, Mcm5, Mcm6 & Mcm7. Note not related to Mcm1 or Mcm10.
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Mcm8
Related to Mcm2-7 family but apparently in distinct
complex. Suggested involvement in elongation step
of DNA replication (although conflicting reports).
Absent in S.Cerevisiae and S.pombe.
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Mcm10
Binds to initiation complex after pre-RC formation
and moves with forks during S
phase.Required
for initiation and elongation stages of DNA
replication. Implicated in chromatin binding of
Cdc45 and DNA pol alpha. Also required for
stability of DNA pol alpha catalytic subunit in S.
cerevisiae.
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MCM9
Related to Mcm2-7 family but apparently in distinct
complex and much less abundant. Suggested
involvement in initiation step of DNA replication.
Only present in vertebrates.
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Mrc1/claspin
Myc
Suggested to binds to origins and act in initiation
after preRC formation (1)
There is a very large literature not reported here covering other aspects of this protein.
1. Dominguez-Sola,D., Ying,C.Y., Grandori,C., Ruggiero,L., Chen,B., Li,M., Galloway,D.A., Gu,W., Gautier,J. and Dalla-Favera,R. (2007) Non-transcriptional control of DNA replication by c-Myc. Nature 448, 445-451.
There is a very large literature not reported here covering other aspects of this protein.
1. Dominguez-Sola,D., Ying,C.Y., Grandori,C., Ruggiero,L., Chen,B., Li,M., Galloway,D.A., Gu,W., Gautier,J. and Dalla-Favera,R. (2007) Non-transcriptional control of DNA replication by c-Myc. Nature 448, 445-451.
Noc3
Nop7/Yph1/Pescadillo
Progression of s phase. Also nucleolar protein
implicated in rRNA processing and ribosome (60S)
biogenesis - suggested link of replication to rDNA
transcription?.
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ORC
Heterohexameric complex composed of Orc1-6. Binds
to DNA and assembles Mcm2-7 complex onto chromatin
(also requires Cdc6 and Cdt1).
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PCNA
Trimeric
protein with ring shaped structure; ring encloses
DNA preventing dissociation. Acts as a
sliding clamp for polymerases delta and epsilon,
thereby improving processivity of replicative
polymerases. Also involved in DNA
repair.
Loaded onto DNA by RFC
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Pif 1
DNA helicase (5’-3’) that may help to promote
replisome progression in some regions of the genome
such as the rRNA genes. Related to
Rrm3.
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recQ helicases
Group of 3’-5’ helicases required for genome
stability. May also help to repair damaged/stalled
replication forks.
(see also recQ4 included with Sld2)
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(see also recQ4 included with Sld2)
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RF-C
Loads PCNA on primed templates and is involved in
the switch between DNA polymerase a and the
replicative polymerases d and e.
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RNaseH
Ribonuclease which digests RNA hybridized to DNA.
Possibly involved in Okazaki fragment
processing.
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RPA
Heterotrimeric single-stranded binding protein.
Stabilizes ssDNA in replication fork. Also involved
in DNA repair and recombination.
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Rrm3
DNA helicase (5’-3’) that may help to promote
replisome progression in some regions of the genome
such as the rRNA genes. Related to
Pif1.
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SIR2
Suggested inhibitor of preRC assembly at a subset
of origins via heterochromatin formation
and/or h4k16 deacetylation. (1)
1. Crampton,A., Chang,F., Pappas,D.L.J., Frisch,R.L. and Weinreich,M. (2008) An ARS element inhibits DNA replication through a SIR2-dependent mechanism. Mol Cell 30, 156-166.
1. Crampton,A., Chang,F., Pappas,D.L.J., Frisch,R.L. and Weinreich,M. (2008) An ARS element inhibits DNA replication through a SIR2-dependent mechanism. Mol Cell 30, 156-166.
Sld2
Functions in initiation of replication. Key
substrate of CDK, phosphorylation promotes
interaction with Dpb11, required for initiation of
replication in S. cerevisiae
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Sld3
Functions in initiation of replication. Key
substrate of CDK, phosphorylation promotes
interaction with Dpb11, required for initiation of
replication in S. cerevisiae.
Higher eukaryotic orthologue not identified.
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Higher eukaryotic orthologue not identified.
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Tof1/Swi1/Tipin
Component of Tof1(swi1/Tim)-Mrc1
(claspin)-Csm3(Swi3/Tipin) replication pausing
checkpoint complex. Probably moves with replication
forks. May maintain integrity of stalled
replication forks.
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Topoisomerases I and II
In humans both proteins are suggested to have a
role in initiation (1) (2)
and ORC binding. In yeast both are thought to have
an elongation role.
There is a very large literature not reported here covering other aspects of these proteins.
1. Abdurashidova,G., Radulescu,S., Sandoval,O., Zahariev,S., Danailov,M.B., Demidovich,A., Santamaria,L., Biamonti,G., Riva,S. and Falaschi,A. (2007) Functional interactions of DNA topoisomerases with a human replication origin. EMBO J 26, 998-1009.
2. Bermejo,R., Doksani,Y., Capra,T., Katou,Y.M., Tanaka,H., Shirahige,K. and Foiani,M. (2007) Top1- and Top2-mediated topological transitions at replication forks ensure fork progression and stability and prevent DNA damage checkpoint activation. Genes Dev 21, 1921-1936.
There is a very large literature not reported here covering other aspects of these proteins.
1. Abdurashidova,G., Radulescu,S., Sandoval,O., Zahariev,S., Danailov,M.B., Demidovich,A., Santamaria,L., Biamonti,G., Riva,S. and Falaschi,A. (2007) Functional interactions of DNA topoisomerases with a human replication origin. EMBO J 26, 998-1009.
2. Bermejo,R., Doksani,Y., Capra,T., Katou,Y.M., Tanaka,H., Shirahige,K. and Foiani,M. (2007) Top1- and Top2-mediated topological transitions at replication forks ensure fork progression and stability and prevent DNA damage checkpoint activation. Genes Dev 21, 1921-1936.
Yra 1
Suggested to bind to origins in S. cerevisiae and
acts in transition from initiation to elongation.
Interacts with Dia2 and polymerase delta
(1)
1. Swaminathan,S., Kile,A.C., MacDonald,E.M. and Koepp,D.M. (2007) Yra1 is required for S phase entry and affects Dia2 binding to replication origins. Mol Cell Biol 27, 4674-4684.
1. Swaminathan,S., Kile,A.C., MacDonald,E.M. and Koepp,D.M. (2007) Yra1 is required for S phase entry and affects Dia2 binding to replication origins. Mol Cell Biol 27, 4674-4684.
Y RNAs
Suggested to be required for DNA replication in
human cells and cell free extracts
(1), (2)
1. Christov,C.P., Gardiner,T.J., Szuts,D. and Krude,T. (2006) Functional requirement of noncoding Y RNAs for human chromosomal DNA replication. Mol Cell Biol 26, 6993-7004.
2. Christov,C.P., Trivier,E. and Krude,T. (2008) Noncoding human Y RNAs are overexpressed in tumours and required for cell proliferation. Br J Cancer 98, 981-988.
1. Christov,C.P., Gardiner,T.J., Szuts,D. and Krude,T. (2006) Functional requirement of noncoding Y RNAs for human chromosomal DNA replication. Mol Cell Biol 26, 6993-7004.
2. Christov,C.P., Trivier,E. and Krude,T. (2008) Noncoding human Y RNAs are overexpressed in tumours and required for cell proliferation. Br J Cancer 98, 981-988.
14-3-3-proteins
Suggested to bind to origins in mammalian cells and
interact with MCM3 and 10 to regulate
replication. (1)
1. Zannis-Hadjopoulos,M., Yahyaoui,W. and Callejo,M. (2008) 14-3-3 cruciform-binding proteins as regulators of eukaryotic DNA replication. Trends Biochem Sci 33, 44-50.
1. Zannis-Hadjopoulos,M., Yahyaoui,W. and Callejo,M. (2008) 14-3-3 cruciform-binding proteins as regulators of eukaryotic DNA replication. Trends Biochem Sci 33, 44-50.