Difference between revisions of "2013 Group 6 Project"

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This is interesting about how the "Anaphase Catastrophe" can be used to treat cancer http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3061280/
 
This is interesting about how the "Anaphase Catastrophe" can be used to treat cancer http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3061280/
 
  
 
== Glossary ==
 
== Glossary ==

Revision as of 16:44, 18 April 2013

2013 Projects: Group 1 | Group 2 | Group 3 | Group 4 | Group 5 | Group 6 | Group 7

Anaphase

Introduction

- Chromosomes split

- sister chromatids move to poles at opposite ends of cell

- Around 1% of cell cycle duration?

- starts with Metaphase to Anaphase transition

- commences with Anaphase promoting complex which marks inhibitory chaperone Securin - Securin inhibits separase

- Importance of Anaphase in living replicating organisms[1]


History

Date Description
1942 PMCID: PMC1078510 - On the Anaphase Movement of Chromosomes
1902 blah
1903 blah
1902 blah
1903 blah

Anaphase

Metaphase to Anaphase transition

Metaphase-to-anaphase transition is tightly controlled by anaphase-promoting complex (APC) motions. APC promotes the degradation of several proteins that inhibit anaphase.[2] The regulatory protein Cdc20 triggers APC/C at the start of the metaphase-anaphase transition. Cdh1 a membrane protein which is able to control the fate of certain cells, triggers anaphase through the G1 stage of the cell cycle. APC/C specifically targets securin(anaphase inhibitor), Early destruction of this inhibitor is coordinated by nuclear transport factors(Nup98 and Rae1), This mechanism is strictly governed to guarantee appropriate timing of degradation. [3]

Mistakes during this process can cause segregation issues leading to the possible demise of the organism. [1]

Metaphase to Anaphase transition


Process of sister chromatid separation

PMID: 10403247 - Sister-chromatid separation at anaphase onset is promoted by cleavage of the cohesin subunit Scc1.

PMID: 22580470 - Sororin is a master regulator of sister chromatid cohesion and separation.

PMID: 14681690 - Two mitotic kinesins cooperate to drive sister chromatid separation during anaphase.

PMID: 9335333 - Cohesins: chromosomal proteins that prevent premature separation of sister chromatids.


Spindle apparatus and Kinetochore

Spindle fibers

Spindle fibers in meiosis are known as the meiotic spindle fibers. Spindle fibers are predominantly made up of microtubules, which are mediated by kinetochore. Kinetochore is a complex protein structure that can be found in the chromosomes that link the chromosomes to the spindle microtubules. [4]

Microtubules can be divided into two categories. Microtubules that interact directly with the kinetochores are known as the kinetochore microtubules (kMTs), whereas microtubules that do not interact with the kinetochores directly, instead they interact with the chromosome arm and other microtubules are known as the non-kinetochore microtubules (non-kMTs). In meiosis, the spindle apparatus are mainly made up of non-kinetochore microtubules. The functions of non-kMTs in meiotic spindles are to maintain a stable chromosome positioning, and to form a proper spindle size. Non-kMTs also play a role in the normal dynamics of kMTs. [5]

The construction of the bipolar spindle involves complex organization of the polymerization dynamics [6]& arrangement of microtubules.

Meiotic spindles need kinesin-5 for the separation of the spindle poles. [7]Inhibition of kinesin-5 after spindle fiber formation causes the structure to collapse. Hence, kinesin-5 is needed in order to maintain the bipolarity of the meiotic spindles. [8]

About the spindle: [9] [10]

Anaphase to Telophase

The kinetochore is a specific zone located on the chromosomes centromeres. [11] During Anaphase chromatids are pulled apart by the microtubules attached to the kinetochore in the direction of the opposite poles. The organisation of these microtubules is critical for regulation of this phase. [12] Anaphase is defined by the the chromatids separating to become a daughter chromosomes. [13] The spindle assembly checkpoint (SAC) is solely responsible for the inhibition of telophase initiation. This checkpoint acts as a government arresting cell processes if there is inadequate supply of kinetochore-microtubule attachments. [14]It should be noted that there are cellular processes that can override and bypass this government through mitotic slippage allowing anaphase lateral entry into telophase. [15]

Metaphase to Anaphase transition

Anaphase in Meiosis

1/ Stages of anaphase in meiosis - then go into depth about proteins and their affect


PMID: 12737807 - Division of the nucleolus and its release of CDC14 during anaphase of meiosis I depends on separase, SPO12, and SLK19.

PMID: 10440376 - Cohesin Rec8 is required for reductional chromosome segregation at meiosis

PMID: 12714746 - Requirement of Cks2 for the first metaphase/anaphase transition of mammalian meiosis

Anaphase in Mitosis

PMID: 12049731 - The anaphase-promoting complex: proteolysis in mitosis and beyond.

Defects resulting from Anaphase malformation

- If the chromosome tips are damaged during anaphase then cytokinesis cannot occur[16] and therefore the cell cannot divide into two daughter cells, not sure if this is in relation to both mitosis and meiosis but should be interesting to further research. The experimental removal of chromosomal tips shows cell division being delayed, the furrow itself being delayed or even regressing from its ready to divide state.

Cytokinesis defects resulting from chromosomal tip damage during Anaphase

- Anaphase-Promoting-Complex mutants of C. elegans demonstrate defects in germline proliferation, the development of the female vulva and male tail and the metaphase to anaphase transition in meiosis I. Therefore irregularities in the APC contribute to physical deformities in this species[17].

- The Anaphase-Promoting-Complex has many important roles in the development, function and survival of the nervous system[18]. Incorrect ACP activity leads to some neurological and psychiatric disorders. Research into the APC's role in neurobiology may grant us ways to use the APC to manage neurological disorders such as mental retardation and autism to even neurodegenerative disorders.

- When the chromosomes do not separate properly in Anaphase, referred to as "nondisjunction" aneuploidy results[19]. This refers to an abnormal number of chromosomes. A well known one is Trisomy 21 or Down's syndrome in which there are three copies of the 21st chromosome[20]. Others include Patau syndrome, Edward's syndrome, Klinefelter syndrome and Turner's syndrome[21][22][23]

- Anaphase bridges can cause mutations such as the structural rearrangement of chromosomes which usually lead to the formation of isochromosomes (chromosomes which, after losing one of their arms are replaced with a copy of another arm) and whole-arm translocations, the loss of the entire chromosome through mitotic spindle detachment or faulty cytokinesis in which the failure to divide results in polyploidy (more than 2 copies of a chromosome) and additional centrosomes which may lead to multipolar spindle formations in future mitosis[24]. The presence of chromatin bridges in Anaphase is also linked to chromosomal instability which may contribute to cancer[25].

          • PMID: 11832245 - The anaphase-promoting complex and separin are required for embryonic anterior-posterior axis formation*****

Current Research

Date Description
2013 PMID: 23566798
2002 blah
2002 blah
2002 blah
2002 blah
2002 blah

This is interesting about how the "Anaphase Catastrophe" can be used to treat cancer http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3061280/

Glossary

Anaphase Promoting Complex - lakjsdlajslkd

Chromatids - jkasjdklas

Chromosome centromere - jkahsdkhas

Cytokinesis - kahsdjkas

Kinetochores - kjasdkjas

Microtubule - kjahsdkas

References

  1. <pubmed>12169670</pubmed>
  2. <pubmed>9425344</pubmed>
  3. <pubmed>17334950</pubmed>
  4. <pubmed>9356457</pubmed>
  5. <pubmed>19706424</pubmed>
  6. <pubmed>9442869</pubmed>
  7. <pubmed> 9268050</pubmed>
  8. <pubmed> 10973989</pubmed>
  9. <pubmed>18235228</pubmed>
  10. <pubmed>10837228</pubmed>
  11. <pubmed>23548928</pubmed>
  12. <pubmed>19269700</pubmed>
  13. <pubmed>23569212</pubmed>
  14. <pubmed>23088867</pubmed>
  15. <pubmed>22321970</pubmed>
  16. <pubmed>20811641</pubmed>
  17. <pubmed>12620985</pubmed>
  18. <pubmed>21439392</pubmed>
  19. <pubmed>18369452</pubmed>
  20. <pubmed>15262983</pubmed>
  21. <pubmed>18927632</pubmed>
  22. <pubmed>21423721</pubmed>
  23. <pubmed>19365562</pubmed>
  24. <pubmed>16082199</pubmed>
  25. <pubmed>15156327</pubmed>





2013 Projects: Group 1 | Group 2 | Group 3 | Group 4 | Group 5 | Group 6 | Group 7

Dr Mark Hill 2013, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G