Faculty Opinions recommendation of A pathway for mitotic chromosome formation.

Author(s):  
Barbara Mellone
2012 ◽  
Vol 125 (6) ◽  
pp. 1591-1604 ◽  
Author(s):  
L. C. Green ◽  
P. Kalitsis ◽  
T. M. Chang ◽  
M. Cipetic ◽  
J. H. Kim ◽  
...  

Science ◽  
2018 ◽  
Vol 359 (6376) ◽  
pp. 648.12-650
Author(s):  
Steve Mao

Science ◽  
2018 ◽  
Vol 359 (6376) ◽  
pp. eaao6135 ◽  
Author(s):  
Johan H. Gibcus ◽  
Kumiko Samejima ◽  
Anton Goloborodko ◽  
Itaru Samejima ◽  
Natalia Naumova ◽  
...  

Mitotic chromosomes fold as compact arrays of chromatin loops. To identify the pathway of mitotic chromosome formation, we combined imaging and Hi-C analysis of synchronous DT40 cell cultures with polymer simulations. Here we show that in prophase, the interphase organization is rapidly lost in a condensin-dependent manner, and arrays of consecutive 60-kilobase (kb) loops are formed. During prometaphase, ~80-kb inner loops are nested within ~400-kb outer loops. The loop array acquires a helical arrangement with consecutive loops emanating from a central “spiral staircase” condensin scaffold. The size of helical turns progressively increases to ~12 megabases during prometaphase. Acute depletion of condensin I or II shows that nested loops form by differential action of the two condensins, whereas condensin II is required for helical winding.


2013 ◽  
Vol 203 (3) ◽  
pp. 471-486 ◽  
Author(s):  
Andrew B. Lane ◽  
Juan F. Giménez-Abián ◽  
Duncan J. Clarke

DNA topoisomerase IIα (Topo IIα) is the target of an important class of anticancer drugs, but tumor cells can become resistant by reducing the association of the enzyme with chromosomes. Here we describe a critical mechanism of chromatin recruitment and exchange that relies on a novel chromatin tether (ChT) domain and mediates interaction with histone H3 and DNA. We show that the ChT domain controls the residence time of Topo IIα on chromatin in mitosis and is necessary for the formation of mitotic chromosomes. Our data suggest that the dynamics of Topo IIα on chromosomes are important for successful mitosis and implicate histone tail posttranslational modifications in regulating Topo IIα.


2020 ◽  
Vol 66 (5) ◽  
pp. 895-899 ◽  
Author(s):  
Jarno Mäkelä ◽  
David Sherratt

Abstract Structural maintenance of chromosomes (SMC) complexes are ancient and conserved molecular machines that organize chromosomes in all domains of life. We propose that the principles of chromosome folding needed to accommodate DNA inside a cell in an accessible form will follow similar principles in prokaryotes and eukaryotes. However, the exact contributions of SMC complexes to bacterial chromosome organization have been elusive. Recently, it was shown that the SMC homolog, MukBEF, organizes and individualizes the Escherichia coli chromosome by forming a filamentous axial core from which DNA loops emanate, similar to the action of condensin in mitotic chromosome formation. MukBEF action, along with its interaction with the partner protein, MatP, also facilitates chromosome individualization by directing opposite chromosome arms (replichores) to different cell halves. This contrasts with the situation in many other bacteria, where SMC complexes organise chromosomes in a way that the opposite replichores are aligned along the long axis of the cell. We highlight the similarities and differences of SMC complex contributions to chromosome organization in bacteria and eukaryotes, and summarize the current mechanistic understanding of the processes.


2012 ◽  
Vol 199 (5) ◽  
pp. 755-770 ◽  
Author(s):  
Kumiko Samejima ◽  
Itaru Samejima ◽  
Paola Vagnarelli ◽  
Hiromi Ogawa ◽  
Giulia Vargiu ◽  
...  

Mitotic chromosome formation involves a relatively minor condensation of the chromatin volume coupled with a dramatic reorganization into the characteristic “X” shape. Here we report results of a detailed morphological analysis, which revealed that chromokinesin KIF4 cooperated in a parallel pathway with condensin complexes to promote the lateral compaction of chromatid arms. In this analysis, KIF4 and condensin were mutually dependent for their dynamic localization on the chromatid axes. Depletion of either caused sister chromatids to expand and compromised the “intrinsic structure” of the chromosomes (defined in an in vitro assay), with loss of condensin showing stronger effects. Simultaneous depletion of KIF4 and condensin caused complete loss of chromosome morphology. In these experiments, topoisomerase IIα contributed to shaping mitotic chromosomes by promoting the shortening of the chromatid axes and apparently acting in opposition to the actions of KIF4 and condensins. These three proteins are major determinants in shaping the characteristic mitotic chromosome morphology.


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