Minichromosome maintenance proteins in eukaryotic chromosome segregation

BioEssays ◽  
2021 ◽  
pp. 2100218
Author(s):  
Gunjan Mehta ◽  
Kaustuv Sanyal ◽  
Suman Abhishek ◽  
Eerappa Rajakumara ◽  
Santanu K. Ghosh
Keyword(s):  
Chromosome Segregation ◽  
Minichromosome Maintenance ◽  
Eukaryotic Chromosome

scholarly journals Basic mechanism of eukaryotic chromosome segregation

2005 ◽  
Vol 360 (1455) ◽  
pp. 609-621 ◽  
Author(s):  
Mitsuhiro Yanagida
Keyword(s):  
Chromosome Segregation ◽  
Protein Modification ◽  
Topoisomerase Ii ◽  
Cell Cycle Control ◽  
Basic Feature ◽  
Basic Mechanism ◽  
Specific Protein ◽  
Eukaryotic Chromosome ◽  
Mitotic Cyclin ◽  
A Cell

We now have firm evidence that the basic mechanism of chromosome segregation is similar among diverse eukaryotes as the same genes are employed. Even in prokaryotes, the very basic feature of chromosome segregation has similarities to that of eukaryotes. Many aspects of chromosome segregation are closely related to a cell cycle control that includes stage-specific protein modification and proteolysis. Destruction of mitotic cyclin and securin leads to mitotic exit and separase activation, respectively. Key players in chromosome segregation are SMC-containing cohesin and condensin, DNA topoisomerase II, APC/C ubiquitin ligase, securin–separase complex, aurora passengers, and kinetochore microtubule destabilizers or regulators. In addition, the formation of mitotic kinetochore and spindle apparatus is absolutely essential. The roles of principal players in basic chromosome segregation are discussed: most players have interphase as well as mitotic functions. A view on how the centromere/kinetochore is formed is described.

scholarly journals csi2p modulates microtubule dynamics and organizes the bipolar spindle for chromosome segregation

2014 ◽  
Vol 25 (24) ◽  
pp. 3900-3908 ◽  
Author(s):  
Judite Costa ◽  
Chuanhai Fu ◽  
V. Mohini Khare ◽  
Phong T. Tran
Keyword(s):  
Fission Yeast ◽  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Microtubule Dynamics ◽  
High Rate ◽  
Spindle Formation ◽  
Bipolar Spindle ◽  
Eukaryotic Chromosome ◽  
Relative Contribution ◽  
Multiple Phenotypes

Proper chromosome segregation is of paramount importance for proper genetic inheritance. Defects in chromosome segregation can lead to aneuploidy, which is a hallmark of cancer cells. Eukaryotic chromosome segregation is accomplished by the bipolar spindle. Additional mechanisms, such as the spindle assembly checkpoint and centromere positioning, further help to ensure complete segregation fidelity. Here we present the fission yeast csi2+. csi2p localizes to the spindle poles, where it regulates mitotic microtubule dynamics, bipolar spindle formation, and subsequent chromosome segregation. csi2 deletion (csi2Δ) results in abnormally long mitotic microtubules, high rate of transient monopolar spindles, and subsequent high rate of chromosome segregation defects. Because csi2Δ has multiple phenotypes, it enables estimates of the relative contribution of the different mechanisms to the overall chromosome segregation process. Centromere positioning, microtubule dynamics, and bipolar spindle formation can all contribute to chromosome segregation. However, the major determinant of chromosome segregation defects in fission yeast may be microtubule dynamic defects.

Regulation of chromosome dynamics by Hsk1/Cdc7 kinase

2013 ◽  
Vol 41 (6) ◽  
pp. 1712-1719 ◽  
Author(s):  
Seiji Matsumoto ◽  
Hisao Masai
Keyword(s):  
Chromosome Segregation ◽  
Meiotic Chromosome ◽  
Centromeric Heterochromatin ◽  
Minichromosome Maintenance ◽  
Replicative Helicase ◽  
Heterochromatin Formation ◽  
Chromosome Dynamics ◽  
Essential Components ◽  
Cdc7 Kinase ◽  
Cell Division Cycle 7

Hsk1 (homologue of Cdc7 kinase 1) of the fission yeast is a member of the conserved Cdc7 (cell division cycle 7) kinase family, and promotes initiation of chromosome replication by phosphorylating Mcm (minichromosome maintenance) subunits, essential components for the replicative helicase. Recent studies, however, indicate more diverse roles for Hsk1/Cdc7 in regulation of various chromosome dynamics, including initiation of meiotic recombination, meiotic chromosome segregation, DNA repair, replication checkpoints, centromeric heterochromatin formation and so forth. Hsk1/Cdc7, with its unique target specificity, can now be regarded as an important modulator of various chromosome transactions.

scholarly journals Condensin DC spreads linearly and bidirectionally from recruitment sites to create loop-anchored TADs in C. elegans

2021 ◽  
Author(s):  
David Sebastian Jimenez ◽  
Jun Kim ◽  
Bhavana Ragipani ◽  
Bo Zhang ◽  
Lena Annika Street ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
X Chromosome ◽  
Molecular Motors ◽  
Sequence Motif ◽  
X Chromosomes ◽  
C Elegans ◽  
Eukaryotic Chromosome ◽  
Multiple Copies

AbstractCondensins are molecular motors that compact DNA for chromosome segregation and gene regulation. In vitro experiments have begun to elucidate the mechanics of condensin function but how condensin loading and translocation along DNA controls eukaryotic chromosome structure in vivo remains poorly understood. To address this question, we took advantage of a specialized condensin, which organizes the 3D conformation of X chromosomes to mediate dosage compensation (DC) in C. elegans. Condensin DC is recruited and spreads from a small number of recruitment elements on the X chromosome (rex). We found that ectopic insertion of rex sites on an autosome leads to bidirectional spreading of the complex over hundreds of kilobases. On the X chromosome, strong rex sites contain multiple copies of a 12-bp sequence motif and act as TAD borders. Inserting a strong rex and ectopically recruiting the complex on the X chromosome or an autosome creates a loop-anchored TAD. Unlike the CTCF system, which controls TAD formation by cohesin, direction of the 12-bp motif does not control the specificity of loops. In an X;V fusion chromosome, condensin DC linearly spreads into V and increases 3D DNA contacts, but fails to form TADs in the absence of rex sites. Finally, we provide in vivo evidence for the loop extrusion hypothesis by targeting multiple dCas9-Suntag complexes to an X chromosome repeat region. Consistent with linear translocation along DNA, condensin DC accumulates at the block site. Together, our results support a model whereby strong rex sites act as insulation elements through recruitment and bidirectional spreading of condensin DC molecules and form loop-anchored TADs.

scholarly journals Adaptive Evolution of Cid, a Centromere-Specific Histone in Drosophila

Genetics ◽  
2001 ◽  
Vol 157 (3) ◽  
pp. 1293-1298 ◽  
Author(s):  
Harmit S Malik ◽  
Steven Henikoff
Keyword(s):  
Drosophila Melanogaster ◽  
Adaptive Evolution ◽  
Chromosome Segregation ◽  
Rapid Evolution ◽  
Histone H3 ◽  
Closely Related Species ◽  
Centromeric Dna ◽  
Eukaryotic Chromosome ◽  
Histone Fold ◽  
Satellite Repeats

Abstract Centromeric DNA is generally composed of large blocks of tandem satellite repeats that change rapidly due to loss of old arrays and expansion of new repeat classes. This extreme heterogeneity of centromeric DNA is difficult to reconcile with the conservation of the eukaryotic chromosome segregation machinery. Histone H3-like proteins, including Cid in Drosophila melanogaster, are a unique chromatin component of centromeres. In comparisons between closely related species of Drosophila, we find an excess of replacement changes that have been fixed since the separation of D. melanogaster and D. simulans, suggesting adaptive evolution. The last adaptive changes appear to have occurred recently, as evident from a reduction in polymorphism in the melanogaster lineage. Adaptive evolution has occurred both in the long N-terminal tail as well as in the histone fold of Cid. In the histone fold, the replacement changes have occurred in the region proposed to mediate binding to DNA. We propose that this rapid evolution of Cid is driven by a response to the changing satellite repeats at centromeres. Thus, centromeric H3-like proteins may act as adaptors between evolutionarily labile centromeric DNA and the conserved kinetochore machinery.

scholarly journals Multi-site phosphorylation of yeast Mif2/CENP-C promotes inner kinetochore assembly

2021 ◽  
Author(s):  
Stephen M Hinshaw ◽  
Yun Quan ◽  
Jiaxi Cai ◽  
Ann Zhou ◽  
Huilin Zhou
Keyword(s):  
Chromosome Segregation ◽  
Regulatory Mechanism ◽  
Phosphorylation Sites ◽  
Biochemical System ◽  
Eukaryotic Chromosome ◽  
Kinetochore Assembly ◽  
Spindle Microtubules ◽  
Pest Region ◽  
Microtubule Poisons ◽  
In Cells

Kinetochores control eukaryotic chromosome segregation by connecting chromosomal centromeres to spindle microtubules. Duplication of centromeric DNA necessitates kinetochore disassembly and subsequent reassembly on the nascent sisters. To search for a regulatory mechanism that controls the earliest steps of kinetochore assembly, we studied Mif2/CENP-C, an essential basal component. We found that Polo-like kinase (Cdc5) and Dbf4-dependent kinase (DDK) phosphorylate the conserved PEST region of Mif2/CENP-C and that this phosphorylation directs inner kinetochore assembly. Mif2 phosphorylation promotes kinetochore assembly in a reconstituted biochemical system, and it strengthens Mif2 localization at centromeres in cells. Disrupting one or more phosphorylation sites in the Mif2-PEST region progressively impairs cellular fitness and sensitizes cells to microtubule poisons. The most severe Mif2-PEST mutations are lethal in cells lacking otherwise non-essential Ctf19 complex factors. These data suggest that multi-site phosphorylation of Mif2/CENP-C is a robust switch that controls inner kinetochore assembly, ensuring accurate chromosome segregation.

scholarly journals Topoisomerases and cancer chemotherapy: recent advances and unanswered questions

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1704 ◽  
Author(s):  
Mary-Ann Bjornsti ◽  
Scott H. Kaufmann
Keyword(s):  
Chromosome Segregation ◽  
Topoisomerase I ◽  
Chromosome Structure ◽  
Eukaryotic Chromosome ◽  
The Past ◽  
Drug Conjugates ◽  
Anticancer Effects ◽  
New Findings ◽  
Recent Developments ◽  
Insight Into

DNA topoisomerases are enzymes that catalyze changes in the torsional and flexural strain of DNA molecules. Earlier studies implicated these enzymes in a variety of processes in both prokaryotes and eukaryotes, including DNA replication, transcription, recombination, and chromosome segregation. Studies performed over the past 3 years have provided new insight into the roles of various topoisomerases in maintaining eukaryotic chromosome structure and facilitating the decatenation of daughter chromosomes at cell division. In addition, recent studies have demonstrated that the incorporation of ribonucleotides into DNA results in trapping of topoisomerase I (TOP1)–DNA covalent complexes during aborted ribonucleotide removal. Importantly, such trapped TOP1–DNA covalent complexes, formed either during ribonucleotide removal or as a consequence of drug action, activate several repair processes, including processes involving the recently described nuclear proteases SPARTAN and GCNA-1. A variety of new TOP1 inhibitors and formulations, including antibody–drug conjugates and PEGylated complexes, exert their anticancer effects by also trapping these TOP1–DNA covalent complexes. Here we review recent developments and identify further questions raised by these new findings.

scholarly journals Evolutionary cell biology of chromosome segregation: insights from trypanosomes

Open Biology ◽  
2013 ◽  
Vol 3 (5) ◽  
pp. 130023 ◽  
Author(s):  
Bungo Akiyoshi ◽  
Keith Gull
Keyword(s):  
Chromosome Segregation ◽  
Cell Biology ◽  
Design Principle ◽  
Genetic Material ◽  
Evolutionary Time ◽  
Origin And Evolution ◽  
Eukaryotic Chromosome ◽  
Evolutionary Origins ◽  
Spindle Microtubules ◽  
Kinetoplastid Parasite

Faithful transmission of genetic material is essential for the survival of all organisms. Eukaryotic chromosome segregation is driven by the kinetochore that assembles onto centromeric DNA to capture spindle microtubules and govern the movement of chromosomes. Its molecular mechanism has been actively studied in conventional model eukaryotes, such as yeasts, worms, flies and human. However, these organisms are closely related in the evolutionary time scale and it therefore remains unclear whether all eukaryotes use a similar mechanism. The evolutionary origins of the segregation apparatus also remain enigmatic. To gain insights into these questions, it is critical to perform comparative studies. Here, we review our current understanding of the mitotic mechanism in Trypanosoma brucei , an experimentally tractable kinetoplastid parasite that branched early in eukaryotic history. No canonical kinetochore component has been identified, and the design principle of kinetochores might be fundamentally different in kinetoplastids. Furthermore, these organisms do not appear to possess a functional spindle checkpoint that monitors kinetochore–microtubule attachments. With these unique features and the long evolutionary distance from other eukaryotes, understanding the mechanism of chromosome segregation in T. brucei should reveal fundamental requirements for the eukaryotic segregation machinery, and may also provide hints about the origin and evolution of the segregation apparatus.

scholarly journals The centromere comes into focus: from CENP-A nucleosomes to kinetochore connections with the spindle

Open Biology ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 200051 ◽  
Author(s):  
Kathryn Kixmoeller ◽  
Praveen Kumar Allu ◽  
Ben E. Black
Keyword(s):  
Chromosome Segregation ◽  
Molecular Complexes ◽  
Molecular Models ◽  
Chromosomal Locus ◽  
Centromeric Chromatin ◽  
Eukaryotic Chromosome ◽  
The Core ◽  
Histone H3 Variant ◽  
Spindle Microtubules ◽  
Insight Into

Eukaryotic chromosome segregation relies upon specific connections from DNA to the microtubule-based spindle that forms at cell division. The chromosomal locus that directs this process is the centromere, where a structure called the kinetochore forms upon entry into mitosis. Recent crystallography and single-particle electron microscopy have provided unprecedented high-resolution views of the molecular complexes involved in this process. The centromere is epigenetically specified by nucleosomes harbouring a histone H3 variant, CENP-A, and we review recent progress on how it differentiates centromeric chromatin from the rest of the chromosome, the biochemical pathway that mediates its assembly and how two non-histone components of the centromere specifically recognize CENP-A nucleosomes. The core centromeric nucleosome complex (CCNC) is required to recruit a 16-subunit complex termed the constitutive centromere associated network (CCAN), and we highlight recent structures reported of the budding yeast CCAN. Finally, the structures of multiple modular sub-complexes of the kinetochore have been solved at near-atomic resolution, providing insight into how connections are made to the CCAN on one end and to the spindle microtubules on the other. One can now build molecular models from the DNA through to the physical connections to microtubules.

Sign in / Sign up

Export Citation Format

Share Document