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.

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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Cdc6

Required for assembly of Mcm2-7 complex at ORC, in conjunction with Cdt1


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Cdk

Cyclin-dependent protein kinase required for initiation of replication and for other subsequent steps .

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Cdt1

Loads Mcm2-7 complex on DNA at at ORC in pre-RC/licensing step. Inhibited by geminin.


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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.

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.

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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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

5’ flap endonuclease and helicase involved in processing Okazaki fragments


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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.
 

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

5’ flap endonuclease involved in processing Okazaki fragments.

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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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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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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.

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.

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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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

Checkpoint adaptor protein. Probable component of replication forks.


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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.

Noc3

Suggested to have a role in initiation

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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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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.
 

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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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.

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.

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.

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.