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@ IJTSRD | Available Online @ www ISSN No: 245 Inte R Cell Cycle Dependent Microtubules A Misreg Aijaz Rashid* Postdoctoral Research Fello National Institutes of Health, NIH *Corresponding author: clbaijaz@ ABSTRACT Microtubules are intrinsic dynamic programmed regulation of microtubu through different phases of cell cycle is numerous proteins known as microtubu proteins (MAPs) and mitotic kinas attachment of microtubules with kin adequate tension generation leads to congression at metaphase plate, that is movement of sister chromatids towards of cells. Impairment, in this process act assembly checkpoint proteins that ham progression and thus maintains genetic s regulation of microtubule dynamics is normal cell cycle progression and aneuploidy. Although microtubules are intrin polymers but programmed regulation o dynamics through different phases of modulated by numerous proteins microtubules associated proteins (MAP kinases[1-3]. Various MAPs present i maintain balance between polymeric an of tubulin and are also responsible for re microtubule cytoskeleton. Microtubu indispensable role in mitosis. Du microtubules attain high dynamic state, increase in microtubule dynamics is ob mitosis. The nucleation rate of micro centrosomes during mitosis shows 7-fold w.ijtsrd.com | Volume – 1 | Issue – 5 | July - Au 56 - 6470 | www.ijtsrd.com | Volum ernational Journal of Trend in Sc Research and Development (IJT International Open Access Journ t Regulation of Microtubule D Associated Proteins (MAPs) an gulation causes Aneuploidy ow, H, USA @gmail.com Shazia Ah Indian Institute of Techno Maharastra, polymers but ule dynamics s modulated by ules associated ses. Proper netochore and chromosomal s followed by opposite poles tivates spindle mper cell cycle stability. Thus, s important in d to prevent nsic dynamic of microtubule f cell cycle is known as Ps) and mitotic inside the cell nd soluble pool eorientat ion of ules perform uring mitosis , 20-100 folds bserved during otubules from d enhancement, compared microtubules[4, 5]. There is dr life of polymerized tubulin interphase cell to merely 10–3 The functional significance after breakdown of nuclear e prometaphase) is strategic k highly dynamic microtubu microtubules display extended and get hold of it by increasin instantaneous shortening to plate[7]. This stochastic search-and-ca by microtubules emanating capture kinetochore and a sim kinetochore of the same chrom by microtubules from other sp amphitelic kinetochore-mic (51).This process involves pr and chromosomal congression plate[8], followed by movem towards opposite poles of movement of chromatids is t shortening of kinetochore- Some motor proteins also movement of chromatids as w congression process [9]. chromosomes is followed by phase of mitosis (telophase), t are formed. Finally cytokines ug 2017 Page: 1269 me - 1 | Issue 5 cientific TSRD) nal Dynamics by nd i ts had ology(IIT) Bombay, , India to the interphase rastic reduction in half- n from 10 minute in 30 s in mitotic cell[5, 6]. of enhanced dynamics envelope (prophase and kinetochore capture by ules. Highly dynamic d search for kinetochore ng in length followed by bring it to metaphase apture process displayed from one spindle pole milar process allows other mosomes to be captured pindle pole, resulting in crotubule attachments roper tension generation n at so called metaphase ment of sister chromotids f cell. The poleward thought to be driven by -attached microtubules. contribute in poleward well as in chromosomal The segregation of de-condensation in last thus two identical nuclei sis takes place where in

Cell Cycle Dependent Regulation of Microtubule Dynamics by Microtubules Associated Proteins (MAPs) and its Misregulation causes Aneuploidy

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Banking occupies one of the most important positions in the modern economic world. It is necessary for trade and industry. Hence it is one of the great agencies of commerce. Modern banking services presence is very helpful to the economic activity and industrial progress of the country. The banking industry is on a major technological up gradation drive after having successfully introduced international standards in their operating norms. It is commonly perceived that technology is important to enhance the quality of customer service and to make it customer friendly. Banking industry is fast growing with the use of technology in the form of ATMs, on line banking, Telephone banking, Mobile banking etc., plastic card is one of the banking products that cater to the needs of retail segment has seen its number grow in geometric progression in recent years. Today, the concept of core banking has made Any Where and any time banking a reality. Along with technology, banking services have also evolved and the delivery of various banking products are carried out through the medium of high technology at a fraction of the cost to the customer. This paper focus on how the technological services in banking sector luring the sustainable development. Aijaz Rashid | Shazia Ahad "Cell Cycle Dependent Regulation of Microtubule Dynamics by Microtubules Associated Proteins (MAPs) and its Misregulation causes Aneuploidy" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-1 | Issue-5 , August 2017, URL: https://www.ijtsrd.com/papers/ijtsrd2409.pdf Paper URL: http://www.ijtsrd.com/management/accounting-and-finance/2409/cell-cycle-dependent-regulation-of-microtubule-dynamics-by-microtubules-associated-proteins-maps-and-its--misregulation-causes-aneuploidy/aijaz-rashid

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Page 1: Cell Cycle Dependent Regulation of Microtubule Dynamics by Microtubules Associated Proteins (MAPs) and its Misregulation causes Aneuploidy

@ IJTSRD | Available Online @ www.ijtsrd.com

ISSN No: 2456

InternationalResearch

Cell Cycle Dependent Regulation of Microtubule Dynamics bMicrotubules Associated Proteins (MAPs) and i

Misregulation

Aijaz Rashid* Postdoctoral Research Fellow

National Institutes of Health, NIH,*Corresponding author: [email protected]

ABSTRACT Microtubules are intrinsic dynamic polymers but programmed regulation of microtubule dynamics through different phases of cell cycle is modulated by numerous proteins known as microtubules associated proteins (MAPs) and mitotic kinases. Proper attachment of microtubules with kinetochore and adequate tension generation leads to chromosomal congression at metaphase plate, that is followed by movement of sister chromatids towards opposite poles of cells. Impairment, in this process activates spindle assembly checkpoint proteins that hamper cell cycle progression and thus maintains genetic stability. Thus, regulation of microtubule dynamics is important in normal cell cycle progression and to prevent aneuploidy.

Although microtubules are intrinsic dynamic polymers but programmed regulation of microtubule dynamics through different phases of cell cycle is modulated by numerous proteins known as microtubules associated proteins (MAPs) and mitotic kinases[1-3]. Various MAPs present inside the cell maintain balance between polymeric and soluble pool of tubulin and are also responsible for reorientatmicrotubule cytoskeleton. Microtubules perform indispensable role in mitosis. During mitosis microtubules attain high dynamic state, 20increase in microtubule dynamics is observed during mitosis. The nucleation rate of microtubules from centrosomes during mitosis shows 7-fold

@ IJTSRD | Available Online @ www.ijtsrd.com | Volume – 1 | Issue – 5 | July - Aug

ISSN No: 2456 - 6470 | www.ijtsrd.com | Volume

International Journal of Trend in Scientific Research and Development (IJTSRD)

International Open Access Journal

Cycle Dependent Regulation of Microtubule Dynamics btubules Associated Proteins (MAPs) and i

egulation causes Aneuploidy

esearch Fellow, NIH, USA

[email protected]

Shazia AhadIndian Institute of Technology(

Maharastra, India

Microtubules are intrinsic dynamic polymers but programmed regulation of microtubule dynamics through different phases of cell cycle is modulated by numerous proteins known as microtubules associated

(MAPs) and mitotic kinases. Proper attachment of microtubules with kinetochore and adequate tension generation leads to chromosomal congression at metaphase plate, that is followed by movement of sister chromatids towards opposite poles

nt, in this process activates spindle assembly checkpoint proteins that hamper cell cycle progression and thus maintains genetic stability. Thus, regulation of microtubule dynamics is important in normal cell cycle progression and to prevent

lthough microtubules are intrinsic dynamic polymers but programmed regulation of microtubule dynamics through different phases of cell cycle is modulated by numerous proteins known as microtubules associated proteins (MAPs) and mitotic

. Various MAPs present inside the cell maintain balance between polymeric and soluble pool of tubulin and are also responsible for reorientation of microtubule cytoskeleton. Microtubules perform indispensable role in mitosis. During mitosis microtubules attain high dynamic state, 20-100 folds increase in microtubule dynamics is observed during mitosis. The nucleation rate of microtubules from

fold

enhancement, compared to the interphase microtubules[4, 5]. There is drastic reduction inlife of polymerized tubulin from 10 minute in interphase cell to merely 10–30 s in mitotic cell

The functional significance of enhanced dynamics after breakdown of nuclear envelope (prophase and prometaphase) is strategic kinetochore capture by highly dynamic microtubules. Highly dynamic microtubules display extended search for kinetochore and get hold of it by increasing in length followed by instantaneous shortening to bring it to metaphase plate[7].

This stochastic search-and-capture process displayed by microtubules emanating from one spindle pole capture kinetochore and a similar process allows other kinetochore of the same chromosomes to be captured by microtubules from other spindle pole, resulting in amphitelic kinetochore-microtubule attachments (51).This process involves proper tension generation and chromosomal congression at so called metaphase plate[8], followed by movement of sister chromotids towards opposite poles of cell. The poleward movement of chromatids is thought to be driven by shortening of kinetochore-Some motor proteins also contribute in poleward movement of chromatids as well as in chromosomal congression process [9]. The segregation of chromosomes is followed by dephase of mitosis (telophase), thus two identical nuclei are formed. Finally cytokinesis takes place where in

Aug 2017 Page: 1269

6470 | www.ijtsrd.com | Volume - 1 | Issue – 5

Scientific (IJTSRD)

International Open Access Journal

Cycle Dependent Regulation of Microtubule Dynamics by tubules Associated Proteins (MAPs) and its

Shazia Ahad Technology(IIT) Bombay,

Maharastra, India

enhancement, compared to the interphase . There is drastic reduction in half-

life of polymerized tubulin from 10 minute in 30 s in mitotic cell[5, 6].

The functional significance of enhanced dynamics after breakdown of nuclear envelope (prophase and prometaphase) is strategic kinetochore capture by highly dynamic microtubules. Highly dynamic

ended search for kinetochore and get hold of it by increasing in length followed by instantaneous shortening to bring it to metaphase

capture process displayed by microtubules emanating from one spindle pole

imilar process allows other kinetochore of the same chromosomes to be captured by microtubules from other spindle pole, resulting in

microtubule attachments (51).This process involves proper tension generation

ssion at so called metaphase , followed by movement of sister chromotids

towards opposite poles of cell. The poleward movement of chromatids is thought to be driven by

-attached microtubules. Some motor proteins also contribute in poleward movement of chromatids as well as in chromosomal

. The segregation of chromosomes is followed by de-condensation in last

s (telophase), thus two identical nuclei are formed. Finally cytokinesis takes place where in

Page 2: Cell Cycle Dependent Regulation of Microtubule Dynamics by Microtubules Associated Proteins (MAPs) and its Misregulation causes Aneuploidy

International Journal of Trend in Scientific Research and Development (IJTSRD) ISSN: 2456-6470

@ IJTSRD | Available Online @ www.ijtsrd.com | Volume – 1 | Issue – 5 | July - Aug 2017 Page: 1313

cytoplasm is divided by the contractile action of actin-myosin ring structures originating at the central

position of cell[10].

Figure 1: Microtubule dynamics and kinetochore capture: After the breakdown of nuclear envelope, microtubules emanating from centrosome called as kinetochore microtubules get hold of kinetochores of chromosomes and align chromosomes at medial position of cell called as metaphasic plate. Microtubule dynamics plays a vital role in kinetochore capture process. Panel A represents a cell in prometaphase and panel B represents cell in metaphase after chromosomes are aligned at metaphase plate. During the progression of cell cycle, attachment of the microtubules to the chromosomes at kinetochores and their metaphasic alignment is of utmost importance because the mitotic cell has to ensure that chromosomes are rightly aligned in metaphase before the anaphase is started to ensure proper segregation of chromosomes to the newly formed daughter cells [11]. However, the failure in this process can lead to aberrant chromosome segregation with unaligned chromosomes which could be a cause for chromosomal instability and aneuploidy[12, 13]. To prevent aneuploidy, a stringent signal transduction pathway operates called as “the spindle assembly checkpoint”. It is a cell cycle surveillance mechanism

which postpones the onset of anaphase till all kinetochores are firmly adhered to spindle microtubules and proper tension is achieved[12]. The spindle checkpoint signaling mechanism comprises of several highly conserved proteins like Mad1, Mad2, Mad3/BubR1, Bub1, Bub3 and Mps1 [13]. During nuclear envelope breakdown kinetochore attachment process starts and spindle checkpoint proteins are activated and recruited to unattached kinetochores and kinetochores devoid of proper tension, resulting in the inhibition of anaphase-promoting-complex/cyclosome (APC/C). An activated spindle checkpoint prevents the beginning of anaphase through inhibition of protein proteolysis and hence prevention of chromatid separation[11, 13]. However, compromised spindle checkpoint mechanism may result in faulty separation of sister chromatids even in the presence of misaligned chromosomes that could be a cause for chromosomal instability (CIN) and hence result in gain or loss of chromosomes called as aneuploidy, a striking feature in human cancer[14]. Significantly, many tumors are known with weakened spindle checkpoint function, thus lack of sustenance of signal for repair of errors[15, 16]. Hence, an impaired spindle checkpoint may directly lead to chromosomal instability and tumorigenesis in human cancer[15].

A

B

Page 3: Cell Cycle Dependent Regulation of Microtubule Dynamics by Microtubules Associated Proteins (MAPs) and its Misregulation causes Aneuploidy

International Journal of Trend in Scientific Research and Development (IJTSRD) ISSN: 2456

@ IJTSRD | Available Online @ www.ijtsrd.com

Figure 2: Mitotic progression: (A) On each kinetochore, when microtubules are adhered and proper tension is generated, the checkpoint proteins are satisfied and released. Then anaphase promoting complex (APC/C) promotes ubquitination of cyclin B and its degradation by 26S proteasome thus providing the biochemical signal for cells to proceed towards anaphase. (B) On the other hand, unattached kinetochore and imbalanced kinetochore tension leads to recruitment of SAC proteins (Mad2, BubR1) to Kinetochore. SAC proteins sequester Cdc20 a cofactor of APC/C, thus inhibiting proteosomal degradation of Cyclin B and Securin. Cyclin B is a protein which regulates early phase of mitosis and securin is inhibitor of separase. Thus, preventproteosomal degradation of Cyclin B and Securin leads to mitotic block.

A

International Journal of Trend in Scientific Research and Development (IJTSRD) ISSN: 2456

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(A) On each kinetochore, when microtubules are adhered and proper tension is generated, the checkpoint proteins are satisfied and released. Then anaphase promoting

itination of cyclin B and its degradation by 26S proteasome thus providing the biochemical signal for cells to proceed towards anaphase. (B) On the other hand, unattached kinetochore and imbalanced kinetochore tension leads

Mad2, BubR1) to Kinetochore. SAC proteins sequester Cdc20 a cofactor of APC/C, thus inhibiting proteosomal degradation of Cyclin B and Securin. Cyclin B is a protein which regulates early phase of mitosis and securin is inhibitor of separase. Thus, prevention of proteosomal degradation of Cyclin B and Securin

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