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Frontiers in Biology

ISSN 1674-7984

ISSN 1674-7992(Online)

CN 11-5892/Q

Front. Biol.    2014, Vol. 9 Issue (6) : 472-480    https://doi.org/10.1007/s11515-014-1334-y
REVIEW
Comparative analysis of chromosome segregation in human, yeasts and trypanosome
Xianxian HAN,Ziyin LI()
Department of Microbiology and Molecular Genetics, University of Texas Medical School, Houston, TX 77030, USA
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Abstract

Chromosome segregation is a tightly regulated process through which duplicated genetic materials are equally partitioned into daughter cells. During the past decades, tremendous efforts have been made to understand the molecular mechanism of chromosome segregation using animals and yeasts as model systems. Recently, new insights into chromosome segregation have gradually emerged using trypanosome, an early branching parasitic protozoan, as a model organism. To uncover the unique aspects of chromosome segregation in trypanosome, which potentially could serve as new drug targets for anti-trypanosome chemotherapy, it is necessary to perform a comparative analysis of the chromosome segregation machinery between trypanosome and its human host. Here, we briefly review the current knowledge about chromosome segregation in human and Trypanosoma brucei, with a focus on the regulation of cohesin and securin degradation triggered by the activation of the anaphase promoting complex/cyclosome (APC/C). We also include yeasts in our comparative analysis since some of the original discoveries were made using budding and fission yeasts as the model organisms and, therefore, these could provide hints about the evolution of the machinery. We highlight both common and unique features in these model systems and also provide perspectives for future research in trypanosome.

Keywords cohesin      separase      securin      anaphase promoting complex      spindle assembly checkpoint      Trypanosoma brucei     
Corresponding Author(s): Ziyin LI   
Just Accepted Date: 09 October 2014   Online First Date: 17 November 2014    Issue Date: 13 January 2015
 Cite this article:   
Xianxian HAN,Ziyin LI. Comparative analysis of chromosome segregation in human, yeasts and trypanosome[J]. Front. Biol., 2014, 9(6): 472-480.
 URL:  
https://academic.hep.com.cn/fib/EN/10.1007/s11515-014-1334-y
https://academic.hep.com.cn/fib/EN/Y2014/V9/I6/472
Fig.1  Regulation of chromosome segregation in eukaryotes. During prometaphase, unattached kinetochores trigger the formation of the mitotic checkpoint complex (MCC), which is composed of Mad2, Bub3, BubR1, and Cdc20. MCC inhibits the activity of the APC/C. Once all kinetochore-microtubule attachment errors are corrected and all chromosomes are aligned at the metaphase plate (metaphase). MCC is no longer formed, thus producing free Cdc20 to activate the APC/C. Activated APC/C ubiquitinates securin, leading to securin degradation by the 26S proteasome. Degradation of securin releases separase, and the latter further cleaves the Scc1 subunit of the cohesin ring complex and produces an open cohesin ring, allowing the bound sister chromatids to separate (anaphase). Cdk1/cyclin B complex also exerts an inhibitory effect on separase, preventing premature chromosome segregation. When cyclin B is ubiquitinated by the activated APC/C and degraded by the 26S proteasome, Cdk1 is inactivated and, consequently, the inhibitory phosphorylation on separase is removed. Degradation of cyclin B also allowed mitotic exit.
H. sapiens S. cerevisiae S. pombe T. brucei
APC1 Apc1 Cut4 APC1
APC2 Apc2 Apc2 APC2
APC3 Cdc27 Nuc2 CDC27
APC4 Apc4 Lid1 APC4
APC5 Apc5 Apc5
APC6 Cdc16 Cut9 CDC16
APC7
APC8 Cdc23 Cut23 CDC23
Apc9
APC10 Doc1 Doc1 DOC1
APC11 Apc11 Apc11 APC11
CDC26 Cdc26 Hcn1
APC13 Swm1 Apc13
Apc14
Mnd2 Apc15
AP2
AP3
Tab.1  Subunit composition of APC/C in different organisms
H. sapiens S. cerevisiae S. pombe T. brucei
Mad1 Mad1 Mad1
Mad2 Mad2 Mad2 Mad2
BubR1 Mad3 Mad3
Bub1 Bub1 Bub1
Bub3 Bub3 Bub3
Mps1 Mps1 Mps1
Tab.2  Spindle assembly checkpoint proteins in different organisms
H. sapiens S. cerevisiae S. pombe T. brucei
Smc1 Smc1 Smc1 Psm1 TbSMC1
Smc3 Smc3 Smc3 Psm3 TbSMC3
Scc1 Rad21 Mcd1/Pds3 Rad21 TbSCC1
Scc3 SA1, SA2 Scc3 Psc3 TbSCC3
Tab.3  Cohesin complex in different organisms
Fig.2  Molecular architecture of the cohesin complex. Smc1 (green) and Smc3 (blue) are each composed of a long coiled-coil arm flanked by an ATP binding head domain and a hinge domain. The N- and C-terminal domains of the kleisin subunit Scc1 (red) bind to the head domains of Smc3 and Smc1, respectively, leading to the formation of a tripartite ring. The fourth subunit of the cohesin complex, Scc3 (purple), binds Scc1.
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