132:. DnaA is highly conserved and has two DNA binding domains. Just upstream to this DnaA box, is three tandem 13-mer sequences. These tandem sequences, labelled L, M, R from 5' to 3' are the bacterial DUEs. Two out of three of these A-T rich regions (M and R) become unwound upon binding of DnaA to DnaA box, via close proximity to unwinding duplex. The final 13-mer sequence L, farthest from this DnaA box eventually gets unwound upon DnaB helicase encircling it. This forms a replication bubble for DNA replication to then proceed.
31:
256:(ARSs) that are transformed and maintained well in a plasmid. Some of these ARSs are seen to act as replication origins. These ARSs are composed of three domains A, B, and C. The A domain is where the ARS consensu s sequence resides, coined an ACS. The B domain contains the DUE. Lastly, the C domain is necessary for facilitating
223:. This binding allows for further factor binding to create a pre-replicative complex (pre-RC). Pre-RC triggered to initiate when cyclin-dependent kinase (CDK) and Dbf4-dependent kinase (DDK) bind to it. Initiation complexes then allow for recruitment of MCM helicase activator Cdc45 and subsequent unwinding of duplex at origin.
306:
They act to initiate strand separation by binding to DUE. DUE-B sequence homologs found among a variety of animal species- fish, amphibians, and rodents. DUE-B's have disordered C-terminal domains that bind to the DUE by recognition of this C-terminus. No other sequence specificity involved in this
195:
Eukaryotic replication mechanisms work in relatively similar ways to that of prokaryotes, but is under more finely-tuned regulation. There is a need to ensure that each DNA molecule is replicated only once and that this is occurring in the proper location at the proper time. Operates in response to
237:
structures can complicate replication initiation. They can block access of DUE-B's to the DUE, thus suppressing transcription initiation. Can impede on rate. The linear nature of eukaryotic DNA, vs prokaryotic circular DNA, though, is easier to unwind its duplex once has been properly unwound from
370:
If there is a severe enough mutation to DUE causing it to no longer be bound to DUE-B, Cdc45 cannot associate and will not bind to c-myc transcription factor. This can be recovered in disease-related (ATTCT)(n) length expansions of the DUE sequence. If DUE activity regained in excess, could cause
102:
start. The unwinding of this duplex strand region is associated with a low free energy requirement, due to helical instability caused by specific base-stacking interactions, in combination with counteracting supercoiling. Negative supercoiling allows the DNA to be stable upon melting, driven by
147:
Unwinding of these three DUEs is a necessary step for DNA replication to initiate. The distant pull from duplex melting at the DnaA box sequence is what induces further melting at the M and R DUE sites. The more distant L site is then unwound by DnaB binding. Unwinding of these 13-mer sites is
77:
organisms, but were first discovered in yeast and bacteria origins, by Huang
Kowalski. The DNA unwinding allows for access of replication machinery to the newly single strands. In eukaryotes, DUEs are the binding site for DNA-unwinding element binding (DUE-B) proteins required for replication
263:
Between species, these ARS sequences are variable, but their A, B, and C domains are well conserved. Any alterations in the DUE (domain B) causes lower overall function of the ARS as a whole in replication initiation. This was found via studies using imino exchange and
340:
though, DUE-Bs can be temporarily phosphorylated to prevent premature replication. DUE-B activity is covalently controlled. The assembly of these DUE-Bs at the DUE regions is dependent on local kinase and phosphatase activity. DUE-B's can also be down-regulated by
280:
Human cells still have very little detailing of their origins. It is known that replication initiates in large initiation zone areas, associated with known proteins like the c-myc and β-globin gene. Ones with DUEs thought to act in nearly same way as yeast cells.
157:
DUEs were experimentally compared through nuclear resonance spectroscopy. In physiological conditions, the opening efficiency of each of the A-T rich sequences differed from one another. Largely due to the different distantly surrounding sequences.
111:
In prokaryotes, most of the time DNA replication is occurring from one single replication origin on one single strand of DNA sequence. Whether this genome is linear or circularized, bacteria have own machinery necessary for replication to occur.
161:
Additionally, melting of AT/TA base pairs were found to be much faster than that of GC/CG pairs (15-240s vs. ~20s). This supports the idea that A-T sequences are evolutionarily favoured in DUE elements due to their ease of unwinding.
276:
DUEs found in some mammalian replication origins to date. In general, very little mammalian origins of replication have been well-analyzed, so difficult to determine how prevalent the DUEs are, in their defined replication origins.
366:
though, maintaining their activity in when altering bases in protein binding sites. In many cases, DUE activity can be partially regained by increasing temperature. Can be regained by the re-addition of DUE site as well.
307:
interaction. Confirmed by inducing mutations along length of DUE-B sequence, but in all cases dimerization abilities remaining intact. Upon binding DNA, C-terminus becomes ordered, imparting a greater stability against
357:
Mutations that impair the unwinding at DUE sites directly impede DNA replication activity. This can be a result of deletions/changes in the DUE region, the addition of reactive reagents, or the addition of specific
186:
contains 9 bases of the 11 base consensus sequence in its oriC, within the 13-mer sequences. These sequences are found exclusively at the single origin of replication; not anywhere else within the genome sequence.
378:
will result. But, activity can be rescued by re-addition of the DUE-B's, even from a different species. This is because DUE-B's are homologous between species. For example, if DUE-B in
311:
degradation. DUE-B's are 209 residues in total, 58 of which are disordered until bound to DUE. DUE-B's hydrolyze ATP In order to function. Also possess similar sequence to
103:
reduction of torsional stress. Found in the replication origins of both bacteria and yeast, as well as present in some mammalian ones. Found to be between 30-100 bp long.
196:
extracellular signals that coordinate initiation of division, differently from tissue to tissue. External signals trigger replication in S phase via production of
82:
flanking the 5' end of DnaA binding domain. The act of unwinding at these A-T rich elements occurs even in absence of any origin binding proteins due to negative
94:
The specific unwinding of the DUE allows for initiation complex assembly at the site of replication on single-stranded DNA, as discovered by Huang
Kowalski. The
326:
In formation of the pre-RC, Cdc45 is localized to the DUE for activity via interaction with a DUE-B. Allowing for duplex unwinding and replication initiation.
124:
is the replication initiator. It gets loaded onto oriC at a DnaA box sequence where it binds and assembles filaments to open duplex and recruit
859:
1073:"The DNA unwinding element in a yeast replication origin functions independently of easily unwound sequences present elsewhere on a plasmid"
291:
Mammals with DUEs have shown evidence of structure-forming abilities that provide single-stranded stability of unwound DNA. These include
374:
In eukaryotes, when DUE-B's are knocked out, the cell will not go into S phase of its cycle, where DNA replication occurs. Increased
901:
808:
775:
680:
253:
288:, found to be associated with a T-ag hexamer, that introduces opposite supercoiling to increase favourability of strand unwinding.
62:. It is A-T rich and denatures easily due to its low helical stability, which allows the single-strand region to be recognized by
257:
323:
secondary structure extending across it. Two of these homodimers come together to form the overall asymmetric DUE-B structure.
407:"The DNA unwinding element: a novel, cis-acting component that facilitates opening of the Escherichia coli replication origin"
86:
forces, making it an energetically favourable action. DUEs are typically found spanning 30-100 bp of replication origins.
208:
136:
63:
924:
Chowdhury A, Liu G, Kemp M, Chen X, Katrangi N, Myers S, Ghosh M, Yao J, Gao Y, Bubulya P, Leffak M (March 2010).
312:
980:
Dhar MK, Sehgal S, Kaul S (May 2012). "Structure, replication efficiency and fragility of yeast ARS elements".
791:
Chodavarapu S, Kaguni JM (2016-01-01). "Replication
Initiation in Bacteria". In Kaguni LS, Oliveira MT (eds.).
248:
148:
independent of oriC-binding proteins. It is the generation of negative supercoiling that causes the unwinding.
1032:"The c-myc DNA-unwinding element-binding protein modulates the assembly of DNA replication complexes in vitro"
201:
178:. A general consensus sequence was made via comparison of conserved bacteria to form an 11 base sequence,
926:"The DNA unwinding element binding protein DUE-B interacts with Cdc45 in preinitiation complex formation"
891:
342:
55:
663:
Potaman VN, Pytlos MJ, Hashem VI, Bissler JJ, Leffak M, Sinden RR (2006). Wells RD, Ashizawa T (eds.).
709:
34:
DNA unwinding at the DUE, allowing for formation of replication fork for DNA replication to occur.
79:
230:
simultaneously. This efficiency is required with the large genomes that they need to replicate.
1102:
1053:
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558:
484:
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418:
265:
227:
175:
152:
226:
Replication in eukaryotes is initiated at multiple sites on the sequence, forming multiple
99:
59:
139:
to find the origin of replication, at sequences termed the origin recognition box (ORB).
713:
624:
950:
925:
819:
672:
422:
363:
292:
1097:
1072:
431:
406:
1119:
732:
698:"DNA helical stability accounts for mutational defects in a yeast replication origin"
697:
125:
83:
1125:
51:
30:
993:
547:"Structure and function of the c-myc DNA-unwinding element-binding protein DUE-B"
238:
nucleosome. Activity of DUE can be modulated by transcription factors like ABF1.
851:
382:
egg are mutated, no DNA replication will occur, but can be saved by addition of
800:
702:
Proceedings of the
National Academy of Sciences of the United States of America
320:
234:
98:
and associated enzymes are now able to bind to the unwound region, creating a
70:
1088:
260:. ARSs are found distributed across 16 chromosomes, repeated every 30–40 kb.
1030:
Casper JM, Kemp MG, Ghosh M, Randall GM, Vaillant A, Leffak M (April 2005).
795:. DNA Replication Across Taxa. Vol. 39. Academic Press. pp. 1–30.
375:
316:
74:
1057:
1048:
1031:
1001:
959:
869:
828:
767:
722:
611:
DePamphilis ML (1993). "Eukaryotic DNA replication: anatomy of an origin".
572:
563:
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472:
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A common yeast model system that well-represents eukaryotic replication is
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632:
440:
941:
359:
346:
330:
308:
212:
95:
379:
337:
220:
336:
DUE-B levels are in consistent quantity, regardless of cell cycle. In
197:
174:, are well-conserved at the origin of replication of all documented
844:
The
Eukaryotic Replisome: A Guide to Protein Structure and Function
17:
29:
667:(Second ed.). Burlington: Academic Press. pp. 447–460.
303:
DNA unwinding element proteins (DUE-Bs) are found in eukaryotes.
78:
initiation. In prokaryotes, DUEs are found in the form of tandem
896:(Second ed.). San Diego: Academic Press. pp. 401–417.
383:
285:
129:
121:
545:
Kemp M, Bae B, Yu JP, Ghosh M, Leffak M, Nair SK (April 2007).
329:
In humans, DUE-B's are 60 amino acids longer than its yeast
846:. Subcellular Biochemistry. Vol. 62. pp. 59–69.
758:
Zyskind JW, Smith DW (2001). Brenner S, Miller JH (eds.).
371:
dysregulated origin formation and cell cycle progression.
27:
Initiation site for the opening of the DNA double helix
315:, and were previously classified a such. DUE-Bs form
333:
counterparts. Both localized mainly in the nucleus.
473:"Base pair opening in three DNA-unwinding elements"
696:Natale DA, Schubert AE, Kowalski D (April 1992).
170:The three 13-mer sequences identified as DUEs in
762:. New York: Academic Press. pp. 1381–1387.
135:Archaea use a simpler homolog of the eukaryotic
50:) is the initiation site for the opening of the
842:Bell SD (2012). "Archaeal Orc1/Cdc6 Proteins".
665:Genetic Instabilities and Neurological Diseases
284:DUE in origin of plasmids in mammalian cells,
219:serving to drive the cell cycle forward into
207:DNA replication in eukaryotes initiates upon
8:
211:(ORC) binding to the origin. This occurs at
362:. DUE sites are relatively insensitive to
1096:
1047:
949:
818:
731:
721:
562:
488:
430:
151:The rates of DNA unwinding in the three
890:Bhagavan, N. V.; Ha, Chung-Eun (2015).
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386:DUE-B's to regain full functionality.
295:, intramolecular triplexes, and more.
1071:Umek RM, Kowalski D (November 1990).
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405:Kowalski D, Eddy MJ (December 1989).
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345:and have been implicated in extended
7:
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751:
1036:The Journal of Biological Chemistry
625:10.1146/annurev.bi.62.070193.000333
551:The Journal of Biological Chemistry
477:The Journal of Biological Chemistry
893:Essentials of Medical Biochemistry
423:10.1002/j.1460-2075.1989.tb08620.x
254:autonomously replicating sequences
25:
673:10.1016/B978-012369462-1/50031-4
930:Molecular and Cellular Biology
471:Coman D, Russu IM (May 2005).
1:
613:Annual Review of Biochemistry
994:10.1016/j.resmic.2012.03.003
258:protein-protein interactions
54:structure of the DNA at the
852:10.1007/978-94-007-4572-8_4
1147:
801:10.1016/bs.enz.2016.03.001
209:origin recognition complex
137:origin recognition complex
64:origin recognition complex
313:aminoacyl-tRNA synthetase
204:(CDK) to form complexes.
120:In bacteria, the protein
982:Research in Microbiology
760:Encyclopedia of Genetics
319:that create an extended
249:Saccharomyces cerevisiae
202:cyclin-dependent kinases
69:DUEs are found in both
1089:10.1093/nar/18.22.6601
1077:Nucleic Acids Research
1049:10.1074/jbc.M404754200
768:10.1006/rwgn.2001.0938
723:10.1073/pnas.89.7.2654
564:10.1074/jbc.M609632200
490:10.1074/jbc.M502773200
35:
353:Mutation Implications
56:origin of replication
40:DNA unwinding element
33:
942:10.1128/MCB.00710-09
299:DUE-binding proteins
714:1992PNAS...89.2654N
80:consensus sequences
166:Consensus Sequence
36:
861:978-94-007-4571-1
228:replication forks
128:with the help of
16:(Redirected from
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1042:(13): 13071–83.
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483:(21): 20216–21.
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411:The EMBO Journal
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266:NMR spectroscopy
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176:enteric bacteria
100:replication fork
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417:(13): 4335–44.
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364:point mutations
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252:. It possesses
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233:In eukaryotes,
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200:which activate
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143:Favourability
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126:DnaB helicase
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60:DNA synthesis
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619:(1): 29–63.
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96:DNA helicase
93:
84:supercoiling
68:
52:double helix
47:
43:
39:
37:
793:The Enzymes
107:Prokaryotes
71:prokaryotic
1120:Categories
390:References
321:beta-sheet
317:homodimers
293:cruciforms
235:nucleosome
217:cell phase
191:Eukaryotes
75:eukaryotic
376:apoptosis
1058:15653697
1002:22504206
960:20065034
870:22918580
829:27241926
573:17264083
499:15784615
360:nuclease
349:stages.
331:ortholog
309:protease
90:Function
1131:Enzymes
1107:2174542
951:2832489
820:5551690
742:1557369
710:Bibcode
633:8352592
441:2556269
380:Xenopus
338:S phase
272:Mammals
221:S phase
198:cyclins
184:E. coli
172:E. coli
154:E. coli
116:Process
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1098:332616
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343:siRNAs
733:48720
242:Yeast
48:DNAUE
1103:PMID
1054:PMID
998:PMID
956:PMID
898:ISBN
866:PMID
856:ISBN
825:PMID
805:ISBN
772:ISBN
738:PMID
677:ISBN
629:PMID
569:PMID
495:PMID
437:PMID
384:HeLa
286:SV40
130:DnaC
122:DnaA
73:and
58:for
1126:DNA
1093:PMC
1085:doi
1044:doi
1040:280
990:doi
986:163
946:PMC
938:doi
848:doi
815:PMC
797:doi
764:doi
728:PMC
718:doi
669:doi
621:doi
559:doi
555:282
485:doi
481:280
427:PMC
419:doi
46:or
44:DUE
18:DUE
1122::
1101:.
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1081:18
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1075:.
1052:.
1038:.
1034:.
1010:^
996:.
984:.
968:^
954:.
944:.
934:30
932:.
928:.
912:^
878:^
864:.
854:.
823:.
813:.
803:.
770:.
750:^
736:.
726:.
716:.
706:89
704:.
700:.
675:.
641:^
627:.
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