31:
165:. The HD gene is found in all human genomes. In the event that a slippage event occurs there can be a large expansion in the tandem repeats of the HD gene. An individual who is not affected by Huntington's disease will have 6-35 tandem repeats at the HD locus. However, an affected individual will have 36- 121 repeats present. The expansion of the HD locus results in a dysfunctional protein leading to Huntington's disease.
206:
SSM events can result in either insertions or deletions. Insertions are thought to be self-accelerating: as repeats grow longer, the probability of subsequent mispairing events increases. Insertions can expand simple tandem repeats by one or more units. In long repeats, expansions may involve two or
173:
Huntington disease is normally progressive and results in movement, cognitive and psychiatric disorders. These disorders can lead to a severe impact on an individual's daily activities, making it hard for proper communication and independent actions to take place. Replication slippage can also lead
160:
Tandem repeats (the main influence for slippage replication) can be found in coding and non-coding regions. If these repeats are found in coding regions then the variations to the polynucleotide sequence can result in the formation of abnormal proteins in eukaryotes. Many human diseases have been
146:
DNA polymerase reassembles its position on the template strand and resumes normal replication, but during the course of reassembling, the polymerase complex backtracks and repeats the insertion of deoxyribonucleotides that were previously added. This results in some repeats found in the template
150:
Nucleotide excision repair proteins are mobilized to this area where one likely outcome is the expansion of nucleotides in the template strand while the other is the absence of nucleotides. Although trinucleotide contraction is possible, trinucleotide expansion occurs more
79:) are found at the site of replication. Tandem repeats are unstable regions of the genome where frequent insertions and deletions of nucleotides can take place, resulting in genome rearrangements.
147:
strand being replicated twice into the daughter strand. This expands the replication region with newly inserted nucleotides. The template and the daughter strand can no longer pair correctly.
87:
into a newly forming DNA strand, plays a significant role in the occurrence of this mutation. When DNA polymerase encounters a direct repeat, it can undergo a replication slippage.
198:( a trinuncleotide expansion in the X25 gene). Therefore, replication slippage leads to a form of trinucleotide expansion which results in serious changes to protein structure.
269:
is thought to account for the evolution of more complex repeat units. Mutations followed by expansion would result in the formation of new types of adjacent
644:
30:
179:
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more units. For example, insertion of a single repeat unit in GAGAGA expands the sequence to GAGAGAGA, while insertion of two repeat units in
60:
strands, resulting in mispairing of the complementary bases. Slipped strand mispairing is one explanation for the origin and evolution of
175:
704:
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95:
605:"Analysis of strand slippage in DNA polymerase expansions of CAG/CTG triplet repeats associated with neurodegenerative disease"
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115:
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Brown TA. Genomes. 2nd edition. Oxford: Wiley-Liss; 2002. Chapter 14, Mutation, Repair and
Recombination. Available from:
183:
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Hartl L.D and Ruvolo M, 2012, Genetic
Analysis of Genes and Genomes, Jones & Bartlett Learning, Burlington, pg. 529
53:
103:
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The newly synthesized strand then detaches from the template strand and pairs with another direct repeat upstream.
382:"A sister-strand exchange mechanism for recA-independent deletion of repeated DNA sequences in Escherichia coli"
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containing a variety of adjacent short tandem repeats are commonly observed in non-protein coding regions of
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The polymerase complex suspends replication and is temporarily released from the template strand.
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that leads to either a trinucleotide or dinucleotide expansion, or sometimes contraction, during
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In the first step, DNA polymerase encounters the direct repeat during the replication process.
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535:"Slipped-strand mispairing can function as a phase variation mechanism in Escherichia coli"
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75:. A slippage event normally occurs when a sequence of repetitive nucleotides (
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Lovett, S.T.; Drapkin, P.T.; Sutera, V.A. Jr.; Gluckman-Peskind, T.J. (1993).
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329:"Slipped-strand mispairing: a major mechanism for DNA sequence evolution"
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reported to be associated with trinucleotide repeat expansions including
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27:
Nucleotide duplications created by DNA polymerase during DNA replication
434:"Replication slippage involves DNA polymerase pausing and dissociation"
307:
94:
processes. Within DNA trinucleotide repeat sequences, the repair of
215:. Genomic regions with a high proportion of repeated DNA sequences (
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486:"Repeat instability during DNA repair: Insights from model systems"
29:
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Rethinking evolution: the revolution that's hiding in plain sight
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Strand slippage may also occur during the DNA synthesis step of
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Slipped strand mispairing has also been shown to function as a
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to other neurodegenerative diseases in humans. These include
83:, the main enzyme to catalyze the polymerization of free
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Petruska J, Hartenstine MJ, Goodman MF (February 1998).
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237:is a cause of a number of human diseases including
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114:may involve strand slippage mispairing leading to
533:Torres-Cruz J, van der Woude MW (December 2003).
194:( trinucleotide expansion in the DMPK gene), and
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182:( trinucleotide expansion in the DRPLA gene),
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432:Viguera, E; Canceill, D; Ehrlich, SD. (2001).
598:
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190:( trinucleotide expansion in the SCA3 gene),
178:( trinucleotide expansion in the AR gene),
8:
588:https://www.ncbi.nlm.nih.gov/books/NBK21114/
186:( trinucleotide expansion in the SCA1gene),
48:) is a mutation process which occurs during
484:Usdin K, House NC, Freudenreich CH (2015).
133:Slippage occurs through five main stages:
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277:could change the simple two- base repeat
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223:) are prone to strand slippage during
346:10.1093/oxfordjournals.molbev.a040442
299:by two subsequent SSM events. Simple
261:Evolution of diverse adjacent repeats
7:
180:dentatorubral–pallidoluysian atrophy
265:The combination of SSM events with
327:Levinson G, Gutman GA (May 1987).
176:spinal and bulbar muscular atrophy
25:
551:10.1128/jb.185.23.6990-6994.2003
289:. This could then be expanded to
125:mechanism in certain bacteria.
235:Trinucleotide repeat expansion
118:when the repair is completed.
116:trinucleotide repeat expansion
1:
490:Crit. Rev. Biochem. Mol. Biol
184:spinocerebellar ataxia type 1
502:10.3109/10409238.2014.999192
731:
398:10.1093/genetics/135.3.631
104:non-homologous end joining
590:Accessed November 3, 2012
38:Slipped strand mispairing
705:Repetitive DNA sequences
450:10.1093/emboj/20.10.2587
301:repetitive DNA sequences
100:homologous recombination
62:repetitive DNA sequences
56:and displacement of the
674:Levinson, Gene (2020).
247:spinocerebellar ataxias
622:10.1074/jbc.273.9.5204
273:units. For example, a
188:Machado-Joseph disease
34:
33:
680:. World Scientific.
660:Huntington's Disease
243:Huntington's disease
169:Disease associations
163:Huntington's disease
112:base excision repair
98:by the processes of
85:deoxyribonucleotides
46:replication slippage
18:Replication slippage
271:short tandem repeat
196:Friedreich's ataxia
108:DNA mismatch repair
251:myotonic dystrophy
239:fragile X syndrome
192:myotonic dystrophy
35:
444:(10): 2587–2595.
202:Self-acceleration
16:(Redirected from
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647:. Archived from
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255:Friedrich ataxia
67:It is a form of
44:, also known as
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710:DNA replication
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333:Mol. Biol. Evol
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225:DNA replication
221:microsatellites
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123:phase variation
73:DNA replication
50:DNA replication
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645:"Stages of HD"
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615:(9): 5204–10.
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545:(23): 6990–4.
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392:(3): 631–642.
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267:point mutation
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217:tandem repeats
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81:DNA polymerase
77:tandem repeats
52:. It involves
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539:J. Bacteriol
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54:denaturation
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151:frequently.
699:Categories
655:2013-10-30
314:References
305:eukaryotic
245:, several
229:DNA repair
96:DNA damage
92:DNA repair
715:Mutation
569:14617664
520:25608779
468:11350948
386:Genetics
69:mutation
631:9478975
511:4454471
416:8293969
407:1205708
355:3328815
308:genomes
156:Effects
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129:Stages
682:ISBN
627:PMID
565:PMID
516:PMID
464:PMID
412:PMID
351:PMID
285:GATA
253:and
227:and
617:doi
613:273
555:PMC
547:doi
543:185
506:PMC
498:doi
454:PMC
446:doi
402:PMC
394:doi
390:135
341:doi
310:.
281:to
110:or
58:DNA
42:SSM
701::
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