scholarly journals Human ANKLE1 is a nuclease specific for branched DNA

2020 ◽  
Author(s):  
Junfang Song ◽  
Alasdair D. J. Freeman ◽  
Axel Knebel ◽  
Anton Gartner ◽  
David M. J. Lilley
Keyword(s):  
Chromosome Segregation ◽  
Cell Cycle Progression ◽  
Genome Integrity ◽  
Substrate Selectivity ◽  
Cycle Progression ◽  
C Elegans ◽  
Dna Junctions ◽  
Sister Chromatids ◽  
Branched Dna ◽  
Late Stages

ABSTRACTAll physical connections between sister chromatids must be broken before cells can divide, and eukaryotic cells have evolved multiple ways in which to process branchpoints connecting DNA molecules separated both spatially and temporally. A single DNA link between chromatids has the potential to disrupt cell cycle progression and genome integrity, so it is highly likely that cells require a nuclease that can process remaining unresolved and hemi-resolved DNA junctions and other branched species at the very late stages of mitosis. We argue that ANKLE1 probably serves this function in human cells (LEM-3 in C. elegans). LEM-3 has previously been shown to be located at the cell mid-body, and we show here that human ANKLE1 is a nuclease that cleaves a range of branched DNA species. It thus has the substrate selectivity consistent with an enzyme required to process a variety of unresolved and hemi-resolved branchpoints in DNA. Our results imply that ANKLE1 acts as a catch-all enzyme of last resort that allows faithful chromosome segregation and cell division to occur.

scholarly journals The Last Chance Saloon

2021 ◽  
Vol 9 ◽  
Author(s):  
Ye Hong ◽  
Hongtao Zhang ◽  
Anton Gartner
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Chromosome Segregation ◽  
Cell Cycle Progression ◽  
Genome Instability ◽  
Genome Integrity ◽  
Cycle Progression ◽  
Chromosome Fragmentation ◽  
C Elegans ◽  
Chromatin Bridges

Accurate chromosome segregation requires the removal of all chromatin bridges, which link chromosomes before cell division. When chromatin bridges fail to be removed, cell cycle progression may halt, or cytokinesis failure and ensuing polyploidization may occur. Conversely, the inappropriate severing of chromatin bridges leads to chromosome fragmentation, excessive genome instability at breakpoints, micronucleus formation, and chromothripsis. In this mini-review, we first describe the origins of chromatin bridges, the toxic processing of chromatin bridges by mechanical force, and the TREX1 exonuclease. We then focus on the abscission checkpoint (NoCut) which can confer a transient delay in cytokinesis progression to facilitate bridge resolution. Finally, we describe a recently identified mechanism uncovered in C. elegans where the conserved midbody associated endonuclease LEM-3/ANKLE1 is able to resolve chromatin bridges generated by various perturbations of DNA metabolism at the final stage of cell division. We also discuss how LEM-3 dependent chromatin bridge resolution may be coordinated with abscission checkpoint (NoCut) to achieve an error-free cleavage, therefore acting as a “last chance saloon” to facilitate genome integrity and organismal survival.

PTTG has a Dual Role of Promotion-Inhibition in the Development of Pituitary Adenomas

2019 ◽  
Vol 26 (11) ◽  
pp. 800-818
Author(s):  
Zujian Xiong ◽  
Xuejun Li ◽  
Qi Yang
Keyword(s):  
Cell Cycle ◽  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Cell Cycle Progression ◽  
Key Factors ◽  
Cycle Progression ◽  
Sister Chromatids ◽  
Regulation Of Cell Cycle ◽  
Late Stages

Pituitary Tumor Transforming Gene (PTTG) of human is known as a checkpoint gene in the middle and late stages of mitosis, and is also a proto-oncogene that promotes cell cycle progression. In the nucleus, PTTG works as securin in controlling the mid-term segregation of sister chromatids. Overexpression of PTTG, entering the nucleus with the help of PBF in pituitary adenomas, participates in the regulation of cell cycle, interferes with DNA repair, induces genetic instability, transactivates FGF-2 and VEGF and promotes angiogenesis and tumor invasion. Simultaneously, overexpression of PTTG induces tumor cell senescence through the DNA damage pathway, making pituitary adenoma possessing the potential self-limiting ability. To elucidate the mechanism of PTTG in the regulation of pituitary adenomas, we focus on both the positive and negative function of PTTG and find out key factors interacted with PTTG in pituitary adenomas. Furthermore, we discuss other possible mechanisms correlate with PTTG in pituitary adenoma initiation and development and the potential value of PTTG in clinical treatment.

A highly conserved centrosomal kinase, AIR-1, is required for accurate cell cycle progression and segregation of developmental factors in Caenorhabditis elegans embryos

Development ◽  
1998 ◽  
Vol 125 (22) ◽  
pp. 4391-4402 ◽  
Author(s):  
J.M. Schumacher ◽  
N. Ashcroft ◽  
P.J. Donovan ◽  
A. Golden
Keyword(s):  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Centrosomal Protein ◽  
C Elegans ◽  
Developmental Factors ◽  
Centrosome Separation ◽  
Spindle Dynamics ◽  
Bipolar Spindles

S. cerevisiae Ipl1, Drosophila Aurora, and the mammalian centrosomal protein IAK-1 define a new subfamily of serine/threonine kinases that regulate chromosome segregation and mitotic spindle dynamics. Mutations in ipl1 and aurora result in the generation of severely aneuploid cells and, in the case of aurora, monopolar spindles arising from a failure in centrosome separation. Here we show that a related, essential protein from C. elegans, AIR-1 (Aurora/Ipl1 related), is localized to mitotic centrosomes. Disruption of AIR-1 protein expression in C. elegans embryos results in severe aneuploidy and embryonic lethality. Unlike aurora mutants, this aneuploidy does not arise from a failure in centrosome separation. Bipolar spindles are formed in the absence of AIR-1, but they appear to be disorganized and are nucleated by abnormal-looking centrosomes. In addition to its requirement during mitosis, AIR-1 may regulate microtubule-based developmental processes as well. Our data suggests AIR-1 plays a role in P-granule segregation and the association of the germline factor PIE-1 with centrosomes.

scholarly journals Non‐redundant functions of H2A.Z.1 and H2A.Z.2 in chromosome segregation and cell cycle progression

EMBO Reports ◽  
2021 ◽  
Author(s):  
Raquel Sales‐Gil ◽  
Dorothee C Kommer ◽  
Ines J Castro ◽  
Hasnat A Amin ◽  
Veronica Vinciotti ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Chromosome Segregation ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Redundant Functions

scholarly journals Cyclin E and CDK-2 regulate proliferative cell fate and cell cycle progression in the C. elegans germline

Development ◽  
2011 ◽  
Vol 138 (11) ◽  
pp. 2223-2234 ◽  
Author(s):  
P. M. Fox ◽  
V. E. Vought ◽  
M. Hanazawa ◽  
M.-H. Lee ◽  
E. M. Maine ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Cell Cycle Progression ◽  
Cyclin E ◽  
Cycle Progression ◽  
C Elegans ◽  
Proliferative Cell

Meiotic cycle checkpoints in mammalian oocytes

Zygote ◽  
1994 ◽  
Vol 2 (4) ◽  
pp. 351-354 ◽  
Author(s):  
Josef Fulka ◽  
Judy Bradshaw ◽  
Robert Moor
Keyword(s):  
Chromosome Segregation ◽  
Cell Cycle Progression ◽  
Mitotic Cell ◽  
Mitotic Cell Cycle ◽  
Cycle Progression ◽  
Daughter Cells ◽  
Chromosomal Segregation ◽  
Nuclear Events ◽  
Last Stage ◽  
Meiotic Cycle

Recent Spectacular achievements have enabled the identification of key molecules responsible for mitotic cell cycle progression through the stages of G1, the gap before DNA replication; S, the phase of DNA synthesis; G2, the gap before chromosome segregation; and M, mitosis itself. The last stage has been most intensively studied, where MPE, maturation promotion factor, has been found responsible for the nuclear events associated with chromosomal segregation and the prodcution of two identical daughter cells (see Murray & Hunt, 1993).

Epigenetic dynamics across the cell cycle

2010 ◽  
Vol 48 ◽  
pp. 107-120 ◽  
Author(s):  
Tony Bou Kheir ◽  
Anders H. Lund
Keyword(s):  
Cell Cycle ◽  
Chromosome Segregation ◽  
Cell Cycle Progression ◽  
Current Knowledge ◽  
Chromatin Condensation ◽  
Chromatin Modifications ◽  
Cycle Progression ◽  
Daughter Cells ◽  
Mammalian Cell Cycle ◽  
Regulate Cell Cycle Progression

Progression of the mammalian cell cycle depends on correct timing and co-ordination of a series of events, which are managed by the cellular transcriptional machinery and epigenetic mechanisms governing genome accessibility. Epigenetic chromatin modifications are dynamic across the cell cycle, and are shown to influence and be influenced by cell-cycle progression. Chromatin modifiers regulate cell-cycle progression locally by controlling the expression of individual genes and globally by controlling chromatin condensation and chromosome segregation. The cell cycle, on the other hand, ensures a correct inheritance of epigenetic chromatin modifications to daughter cells. In this chapter, we summarize the current knowledge on the dynamics of epigenetic chromatin modifications during progression of the cell cycle.

scholarly journals MLL5 maintains spindle bipolarity by preventing aberrant cytosolic aggregation of PLK1

2016 ◽  
Vol 212 (7) ◽  
pp. 829-843 ◽  
Author(s):  
Wei Zhao ◽  
Jie Liu ◽  
Xiaoming Zhang ◽  
Lih-Wen Deng
Keyword(s):  
Chromosome Segregation ◽  
Cell Cycle Progression ◽  
Genomic Stability ◽  
Binding Motif ◽  
Wild Type ◽  
Microtubule Organizing Center ◽  
Cycle Progression ◽  
Molecular Studies ◽  
Organizing Center ◽  
Do So

Faithful chromosome segregation with bipolar spindle formation is critical for the maintenance of genomic stability. Perturbation of this process often leads to severe mitotic failure, contributing to tumorigenesis. MLL5 has been demonstrated to play vital roles in cell cycle progression and the maintenance of genomic stability. Here, we identify a novel interaction between MLL5 and PLK1 in the cytosol that is crucial for sustaining spindle bipolarity during mitosis. Knockdown of MLL5 caused aberrant PLK1 aggregation that led to acentrosomal microtubule-organizing center (aMTOC) formation and subsequent spindle multipolarity. Further molecular studies revealed that the polo-box domain (PBD) of PLK1 interacted with a binding motif on MLL5 (Thr887-Ser888-Thr889), and this interaction was essential for spindle bipolarity. Overexpression of wild-type MLL5 was able to rescue PLK1 mislocalization and aMTOC formation in MLL5-KD cells, whereas MLL5 mutants incapable of interacting with the PBD failed to do so. We thus propose that MLL5 preserves spindle bipolarity through maintaining cytosolic PLK1 in a nonaggregated form.

scholarly journals Retinoblastoma Protein Enhances the Fidelity of Chromosome Segregation Mediated by hsHec1p

2000 ◽  
Vol 20 (10) ◽  
pp. 3529-3537 ◽  
Author(s):  
Lei Zheng ◽  
Yumay Chen ◽  
Daniel J. Riley ◽  
Phang-Lang Chen ◽  
Wen-Hwa Lee
Keyword(s):  
Dna Binding ◽  
Chromosome Segregation ◽  
Cell Cycle Progression ◽  
Retinoblastoma Protein ◽  
Binding Activity ◽  
Yeast Cells ◽  
Temperature Sensitive ◽  
Cycle Progression ◽  
Dna Binding Activity ◽  
M Phase

ABSTRACT Retinoblastoma protein (Rb) plays important roles in cell cycle progression and cellular differentiation. It may also participate in M phase events, although heretofore only circumstantial evidence has suggested such involvement. Here we show that Rb interacts, through an IxCxE motif and specifically during G2/M phase, with hsHec1p, a protein essential for proper chromosome segregation. The interaction between Rb and hsHec1p was reconstituted in a yeast strain in which human hsHEC1 rescues the null mutation of scHEC1. Expression of Rb reduced chromosome segregation errors fivefold in yeast cells sustained by a temperature-sensitive (ts) hshec1-113 allele and enhanced the ability of wild-type hsHec1p to suppress lethality caused by a ts smc1mutation. The interaction between Hec1p and Smc1p was important for the specific DNA-binding activity of Smc1p. Expression of Rb restored part of the inactivated function of hshec1-113p and thereby increased the DNA-binding activity of Smc1p. Rb thus increased the fidelity of chromosome segregation mediated by hsHec1p in a heterologous yeast system.

scholarly journals Physically asymmetric division of the C. elegans zygote ensures invariably successful embryogenesis

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Radek Jankele ◽  
Rob Jelier ◽  
Pierre Gönczy
Keyword(s):  
Cell Fate ◽  
Cell Cycle Progression ◽  
Cell Lineage ◽  
External Compression ◽  
Cycle Progression ◽  
Spindle Positioning ◽  
C Elegans ◽  
Daughter Cells ◽  
Asymmetric Divisions ◽  
Cell Positioning

Asymmetric divisions that yield daughter cells of different sizes are frequent during early embryogenesis, but the importance of such a physical difference for successful development remains poorly understood. Here, we investigated this question using the first division ofCaenorhabditis elegansembryos, which yields a large AB cell and a small P1cell. We equalized AB and P1sizes using acute genetic inactivation or optogenetic manipulation of the spindle positioning protein LIN-5. We uncovered that only some embryos tolerated equalization, and that there was a size asymmetry threshold for viability. Cell lineage analysis of equalized embryos revealed an array of defects, including faster cell cycle progression in P1descendants, as well as defects in cell positioning, division orientation, and cell fate. Moreover, equalized embryos were more susceptible to external compression. Overall, we conclude that unequal first cleavage is essential for invariably successful embryonic development ofC. elegans.

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