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{{short description|Chromosome attachment pattern in cytogenetics}}
'''Syntelic attachment''' occurs when both sister [[chromosome]]s are attached to a single [[spindle pole]].<ref>{{cite web|title=Examining chromosome-microtubule attachment|url=http://www.kapoorlab.com/research_3_2_1.html|archive-url=https://web.archive.org/web/20100903140156/http://www.kapoorlab.com/research_3_2_1.html|archive-date=3 September 2010}}</ref><ref>{{cite journal|last1=London|first1=Nitobe|last2=Biggins|first2=Sue|title=Signalling dynamics in the spindle checkpoint response|journal=Nature Reviews Molecular Cell Biology|date=1 November 2014|volume=15|issue=11|pages=736–748|doi=10.1038/nrm3888|pmid=25303117|language=en|pmc=4283840}}</ref>

Normal [[cell division]] distributes the genome equally between two daughter cells, with each chromosome attaching to an ovoid structure called the spindle. During the division process, errors commonly occur in attaching the chromosomes to the spindle, estimated to affect 86 to 90 percent of chromosomes.<ref name="sciencedaily">{{cite journal|title=Molecular forces are key to proper cell division|website=www.sciencedaily.com|date=January 21, 2013|url=https://www.sciencedaily.com/releases/2013/01/130121103303.htm|access-date=3 February 2017|publisher=University of Massachusetts Amherst}}</ref>

Such attachment errors are common during the early stages of spindle formation, but they are mostly corrected before the start of [[anaphase]].<ref>{{cite web|title=CELLS Interactive Glossary: Syntelic attachment|url=http://bioscience.jbpub.com/cells/glossary.cfm?term=Syntelic%20attachment&step=5|website=bioscience.jbpub.com|publisher=Jones and Bartlett Publishers|access-date=3 February 2017}}</ref>
Successful cell division requires identification and correction of any dangerous errors before the cell splits in two.<ref name="sciencedaily"/>
If the syntelic attachment continues, it causes both sister [[chromatid]]s to be segregated to a single daughter cell.<ref>{{cite journal|last1=Walczak|first1=Claire E.|last2=Cai|first2=Shang|last3=Khodjakov|first3=Alexey|title=Mechanisms of chromosome behaviour during mitosis|journal=Nature Reviews Molecular Cell Biology|date=20 January 2010|volume=11|issue=2|pages=91–102|doi=10.1038/nrm2832|pmid=20068571|pmc=2893392}}</ref>

==Causes==

[[Microtubule]]s extend from the [[spindle apparatus|spindle poles]] and attach to the first [[kinetochore]] they encounter.<ref name=":0">{{cite journal |last1=Nicklas |first1=R. Bruce |title=How Cells Get the Right Chromosomes |journal=Science |date=1997 |volume=275 |issue=5300 |pages=632–637 |doi=10.1126/science.275.5300.632 |pmid=9005842|s2cid=30090031 }}</ref> Because this process is stochastic and not facilitated or directed, the first microtubules to come into contact with a kinetochore may not have originated at the correct spindle pole.<ref name=":1">{{cite journal |last1=Banerjee |first1=Anand |last2=Adames |first2=Neil |last3=Peccoud |first3=Jean |last4=Tyson |first4=John J. |title=A stochastic model for error correction of kinetochore-microtubule attachments in budding yeast |journal=PLOS ONE |date=2020 |volume=15 |issue=8 |article-number=e0236293 |doi=10.1371/journal.pone.0236293 |pmid=32760074|pmc=7410253 |bibcode=2020PLoSO..1536293B |hdl=10919/100303 |hdl-access=free |doi-access=free }}</ref> Normally, the sister kinetochores are on opposing sides of the [[chromosome]]s, facing outward toward their respective spindle poles.<ref name=":2">{{cite journal |last1=Lončarek |first1=Jadranka |last2=Kisurina-Evgenieva |first2=Olga |last3=Vinogradova |first3=Tatiana |last4=Hergert |first4=Polla |last5=La Terra |first5=Sabrina |last6=Kapoor |first6=Tarun M. |last7=Khodjakov |first7=Alexey |title=The centromere geometry essential for keeping mitosis error free is controlled by spindle forces |journal=Nature |date=2007 |volume=450 |issue=7170 |pages=745–749 |doi=10.1038/nature06344 |pmid=18046416|pmc=2586812 |bibcode=2007Natur.450..745L }}</ref> This arrangement enhances the likelihood of properly bi-oriented chromosomes and is sometimes referred to as a mechanism for 'avoidance' of syntelic attachment.<ref name=":2" /><ref name=":3">{{cite journal |last1=Dewar |first1=Hilary |last2=Tanaka |first2=Kozo |last3=Nasmyth |first3=Kim |last4=Tanaka |first4=Tomoyuki U. |title=Tension between two kinetochores suffices for their bi-orientation on the mitotic spindle |journal=Nature |date=2004 |volume=428 |issue=6978 |pages=93–97 |doi=10.1038/nature02328 |pmid=14961024|bibcode=2004Natur.428...93D |s2cid=4418232 }}</ref> However, sometimes the kinetochores are found on the same side of the [[centromere]], and this error cannot be corrected stochastically.<ref name=":2" /> Instead, the spindle must actively exert forces on one of the two kinetochores to relocate it to the proper, outer edge of the centromere.<ref name=":2" /> If the geometry and orientation of the two kinetochores is not corrected, the cells can still effectively achieve bi-orientation through the employment of error correction mechanisms.<ref name=":3" />

[[Polyploidy|Polyploid]] cells, and [[tetraploid]]s in particular, experience an increased number of syntelic attachments, which contributes to their [[genomic instability]].<ref name=":4">{{cite journal |last1=Storchová |first1=Zuzana |last2=Breneman |first2=Amanda |last3=Cande |first3=Jessica |last4=Dunn |first4=Joshua |last5=Burbank |first5=Kendra |last6=O'Toole |first6=Eileen |last7=Pellman |first7=David |title=Genome-wide genetic analysis of polyploidy in yeast |journal=Nature |date=2006 |volume=443 |issue=7111 |pages=541–547 |doi=10.1038/nature05178 |pmid=17024086|bibcode=2006Natur.443..541S |s2cid=4421746 }}</ref> This phenomenon of increased rates of syntelic attachment in polyploids is thought to result from an inability to scale the mitotic spindle and kinetochore architecture to accommodate the increase in cell size.<ref name=":4" /> Therefore, scaling defects between the genome and cellular architecture, which often occur in [[cancer]], likely result in high rates of syntelic attachment.<ref name=":4" />

==Error correction==

Error correction is closely tied to the [[spindle assembly checkpoint]] (SAC), which oversees the progression through [[mitosis]] and can halt the cell in [[metaphase]] until proper bi-orientation of all chromosomes is achieved.<ref name=":5">{{cite journal |last1=Khodjakov |first1=Alexey |last2=Pines |first2=Jonathon |title=Centromere tension: a divisive issue |journal=Nature Cell Biology |date=2010 |volume=12 |issue=10 |pages=919–923 |doi=10.1038/ncb1010-919 |pmid=20885417|pmc=3052926 }}</ref> Initial attachments occur randomly, and the cell destabilizes any incorrect microtubule-kinetochore interactions. Subsequent rounds of undirected attachment and destabilization occur until each kinetochore is attached to the correct spindle pole.

[[Tension (physics)|Tension]] was quickly identified as an important component of the error-sensing mechanism and likely of the spindle assembly checkpoint.<ref name=":0" /><ref name=":5" /> Ipl1 in [[yeast]] and its functional [[homolog]], [[Aurora B]], in [[metazoa]]ns aid in tension detection and destabilization of errant attachments.<ref name=":5" /><ref name=":6">{{cite journal |last1=Lampson |first1=Michael A. |last2=Cheeseman |first2=Iain M. |title=Sensing centromere tension: Aurora B and the regulation of kinetochore function |journal=Trends in Cell Biology |date=2011 |volume=21 |issue=3 |pages=133–140 |doi=10.1016/j.tcb.2010.10.007 |pmid=21106376|pmc=3049846 |hdl=1721.1/98881 |hdl-access=free }}</ref> Aurora B is found at the centromere, between the two kinetochores.<ref name=":5" /> In the absence of tension, Aurora B can [[phosphorylate]] substrates at the kinetochores, leading to destabilization of the attached microtubules.<ref name=":5" /> Properly attached microtubules induce tension, pulling the kinetochore far enough away from Aurora B so as to prevent phosphorylation of kinetochore components.<ref name=":5" /> Following destabilization, the kinetochore can form new spindle attachments, and if the new attachments result in chromosome bi-orientation, they will remain.<ref name=":6" /> Correct attachments that induce tension are more likely to occur when the kinetochores are geometrically positioned on opposite sides of the centromere.<ref name=":1" />

Robust destabilization by Ipl1/Aurora B in the absence of tension leads to a specific challenge: the initial establishment of bi-orientation, prior to the buildup of tension, would be sensitive to Ipl1/Aurora B activity.<ref name=":7">{{cite journal |last1=Tubman |first1=Emily S. |last2=Biggins |first2=Sue |last3=Odde |first3=David J. |title=Stochastic Modeling Yields a Mechanistic Framework for Spindle Attachment Error Correction in Budding Yeast Mitosis |journal=Cell Systems |date=2017 |volume=4 |issue=6 |pages=645–650.e5 |doi=10.1016/j.cels.2017.05.003 |pmid=28601560|pmc=5533192 }}</ref> This is referred to as the initiation problem of biorientation (IPBO), and is resolved by implementing a delay between sensing the tension and destabilizing the attachment.<ref name=":7" /> Modeling has indicated that such a delay could be introduced if the rate of Ipl1/Aurora B [[kinase]] activity is slower than that of the counteracting [[phosphatase]] activity at the kinetochore.<ref name=":7" /> The time delay allows for tension to be established at bi-oriented chromosomes, so that only syntelic attachments are phosphorylated and destabilized.<ref name=":7" />

==Consequences==

Syntelic attachment is not uncommon in early [[metaphase]], and can often be resolved by error correction mechanisms that are well-conserved across [[metazoa]]ns.<ref name=":6" /> If syntelic attachment is left uncorrected, for example if the [[spindle assembly checkpoint]] does not successfully pause cells in metaphase, the [[chromosome]]s will not segregate correctly.<ref name=":6" /> This failure to properly segregate results in [[aneuploidy]], which can lead to errors in [[embryonic development|development]] or [[cancer]].<ref name=":8">{{cite journal |last1=Lampson |first1=Michael A. |last2=Grishchuk |first2=Ekaterina L. |title=Mechanisms to Avoid and Correct Erroneous Kinetochore-Microtubule Attachments |journal= Biology|date=2017 |volume=6 |issue=1 |page=1 |doi=10.3390/biology6010001 |pmid=28067761|pmc=5371994 |doi-access=free }}</ref> Interestingly, segregation errors that result from syntelic attachment often occur without visible [[anaphase lag|lagging]].<ref name=":9">{{cite journal |last1=Thompson |first1=Sarah L. |last2=Compton |first2=Duane A. |title=Chromosome missegregation in human cells arises through specific types of kinetochore–microtubule attachment errors |journal=PNAS |date=2011 |volume=108 |issue=44 |pages=17974–17978 |doi=10.1073/pnas.1109720108 |pmid=21997207|pmc=3207692 |bibcode=2011PNAS..10817974T |doi-access=free }}</ref> In contrast, merotelic attachments will cause chromosome lagging during [[anaphase]], but will often segregate correctly and not result in aneuploidy.<ref name=":8" /><ref name=":9" />

==See also==

*[[Spindle checkpoint]]
*[[Kinetochore]]
*[[Spindle apparatus]]

==References==
{{reflist}}

[[Category:Chromosomes]]
[[Category:Genetics]]

Syntelic - История изменений

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