scholarly journals NEIL3 Repairs Telomere Damage during S Phase to Secure Chromosome Segregation at Mitosis

Cell Reports ◽  
2017 ◽  
Vol 20 (9) ◽  
pp. 2044-2056 ◽  
Author(s):  
Jia Zhou ◽  
Jany Chan ◽  
Marie Lambelé ◽  
Timur Yusufzai ◽  
Jason Stumpff ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
S Phase

scholarly journals The yeast S phase checkpoint enables replicating chromosomes to bi-orient and restrain spindle extension during S phase distress

2005 ◽  
Vol 168 (7) ◽  
pp. 999-1012 ◽  
Author(s):  
Jeff Bachant ◽  
Shannon R. Jessen ◽  
Sarah E. Kavanaugh ◽  
Candida S. Fielding
Keyword(s):  
Dna Replication ◽  
Chromosome Segregation ◽  
Replication Fork ◽  
S Phase ◽  
Origin Of Replication ◽  
Independent Manner ◽  
Checkpoint Signaling ◽  
Hydroxyurea Treatment ◽  
Chromatid Cohesion ◽  
S Phase Checkpoint

The budding yeast S phase checkpoint responds to hydroxyurea-induced nucleotide depletion by preventing replication fork collapse and the segregation of unreplicated chromosomes. Although the block to chromosome segregation has been thought to occur by inhibiting anaphase, we show checkpoint-defective rad53 mutants undergo cycles of spindle extension and collapse after hydroxyurea treatment that are distinct from anaphase cells. Furthermore, chromatid cohesion, whose dissolution triggers anaphase, is dispensable for S phase checkpoint arrest. Kinetochore–spindle attachments are required to prevent spindle extension during replication blocks, and chromosomes with two centromeres or an origin of replication juxtaposed to a centromere rescue the rad53 checkpoint defect. These observations suggest that checkpoint signaling is required to generate an inward force involved in maintaining preanaphase spindle integrity during DNA replication distress. We propose that by promoting replication fork integrity under these conditions Rad53 ensures centromere duplication. Replicating chromosomes can then bi-orient in a cohesin-independent manner to restrain untimely spindle extension.

Morphology and behaviour of dinoflagellate chromosomes during the cell cycle and mitosis

2000 ◽  
Vol 113 (7) ◽  
pp. 1231-1239 ◽  
Author(s):  
Y. Bhaud ◽  
D. Guillebault ◽  
J. Lennon ◽  
H. Defacque ◽  
M.O. Soyer-Gobillard ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Cell Cycle ◽  
Confocal Microscopy ◽  
Nuclear Envelope ◽  
Chromosome Segregation ◽  
Morphological Changes ◽  
S Phase ◽  
Chromosome Behaviour ◽  
Double Number ◽  
Do So

The morphology and behaviour of the chromosomes of dinoflagellates during the cell cycle appear to be unique among eukaryotes. We used synchronized and aphidicolin-blocked cultures of the dinoflagellate Crypthecodinium cohnii to describe the successive morphological changes that chromosomes undergo during the cell cycle. The chromosomes in early G(1) phase appeared to be loosely condensed with numerous structures protruding toward the nucleoplasm. They condensed in late G(1), before unwinding in S phase. The chromosomes in cells in G(2) phase were tightly condensed and had a double number of arches, as visualised by electron microscopy. During prophase, chromosomes elongated and split longitudinally, into characteristic V or Y shapes. We also used confocal microscopy to show a metaphase-like alignment of the chromosomes, which has never been described in dinoflagellates. The metaphase-like nucleus appeared flattened and enlarged, and continued to do so into anaphase. Chromosome segregation occurred via binding to the nuclear envelope surrounding the cytoplasmic channels and microtubule bundles. Our findings are summarized in a model of chromosome behaviour during the cell cycle.

scholarly journals DNA replication and spindle checkpoints cooperate during S phase to delay mitosis and preserve genome integrity

2014 ◽  
Vol 204 (2) ◽  
pp. 165-175 ◽  
Author(s):  
Maria M. Magiera ◽  
Elisabeth Gueydon ◽  
Etienne Schwob
Keyword(s):  
Dna Replication ◽  
Chromosome Segregation ◽  
Replication Stress ◽  
S Phase ◽  
Genome Integrity ◽  
Replication Forks ◽  
Mitotic Entry ◽  
Transient Activation ◽  
Spindle Checkpoints ◽  
Spindle Assembly Checkpoints

Deoxyribonucleic acid (DNA) replication and chromosome segregation must occur in ordered sequence to maintain genome integrity during cell proliferation. Checkpoint mechanisms delay mitosis when DNA is damaged or upon replication stress, but little is known on the coupling of S and M phases in unperturbed conditions. To address this issue, we postponed replication onset in budding yeast so that DNA synthesis is still underway when cells should enter mitosis. This delayed mitotic entry and progression by transient activation of the S phase, G2/M, and spindle assembly checkpoints. Disabling both Mec1/ATR- and Mad2-dependent controls caused lethality in cells with deferred S phase, accompanied by Rad52 foci and chromosome missegregation. Thus, in contrast to acute replication stress that triggers a sustained Mec1/ATR response, multiple pathways cooperate to restrain mitosis transiently when replication forks progress unhindered. We suggest that these surveillance mechanisms arose when both S and M phases were coincidently set into motion by a unique ancestral cyclin–Cdk1 complex.

Pre-meiotic S phase is linked to reductional chromosome segregation and recombination

Nature ◽  
2001 ◽  
Vol 409 (6818) ◽  
pp. 359-363 ◽  
Author(s):  
Yoshinori Watanabe ◽  
Shihori Yokobayashi ◽  
Masayuki Yamamoto ◽  
Paul Nurse
Keyword(s):  
Chromosome Segregation ◽  
S Phase

scholarly journals Oocyte-specific deletion of Hdac8 in mice reveals stage-specific effects on fertility

Reproduction ◽  
2019 ◽  
Vol 157 (3) ◽  
pp. 305-316 ◽  
Author(s):  
Vijay Pratap Singh ◽  
Wei-Ting Yueh ◽  
Jennifer L Gerton ◽  
Francesca E Duncan
Keyword(s):  
Chromosome Segregation ◽  
Histone Deacetylases ◽  
Reproductive Function ◽  
S Phase ◽  
Female Fertility ◽  
Specific Expression ◽  
Specific Effects ◽  
Chromatid Cohesion ◽  
Class 1 ◽  
Specific Deletion

Eighteen histone deacetylases exist in mammals. The class 1 histone deacetylases HDAC1 and HDAC2 are important for oogenesis and fertility in mice, likely via their effects on histones. The reproductive function of HDAC8, another class 1 enzyme, has not been explored. One key target of HDAC8 is the SMC3 subunit of cohesin, an essential complex mediating sister chromatid cohesion and chromosome segregation. In current models, HDAC8 activity is required for SMC3 recycling, but this function should be dispensable in oocytes since cohesion is established during pre-meiotic S phase and maintained until meiotic resumption during ovulation. Whether other oocyte-specific HDAC8-mediated deacetylation events are required for oogenesis and female fertility is unknown. We used two Cre drivers to remove Hdac8 at specific stages of oocyte development to address whether HDAC8 is required for female fertility in mice. When HDAC8 was knocked out in oocytes in primary and later stage follicles (Zp3-Cre), oogenesis and folliculogenesis appeared normal and mice were fertile. However, females were subfertile when HDAC8 was knocked out prior to pre-meiotic S phase and cohesion establishment (Vasa-Cre). This subfertility was independent of chromosome segregation errors during meiosis but rather appeared to be the result of defects in oogenesis that resulted in smaller fully grown oocytes with a reduced ability to resume meiosis. In all cases, we did not observe compensatory changes in HDAC1, HDAC2 and HDAC3 levels. Thus, although oocyte-specific expression of HDAC8 is not essential for mouse oogenesis after meiotic S phase, it contributes to optimal fertility. We infer that oocyte-specific expression of the deacetylase HDAC8 is required early in oogenesis for optimal fertility.

scholarly journals A Meiosis-Specific Cyclin Regulated by Splicing Is Required for Proper Progression through Meiosis

2005 ◽  
Vol 25 (15) ◽  
pp. 6330-6337 ◽  
Author(s):  
Jordi Malapeira ◽  
Alberto Moldón ◽  
Elena Hidalgo ◽  
Gerald R. Smith ◽  
Paul Nurse ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Synthesis ◽  
Chromosome Segregation ◽  
Mitotic Cycle ◽  
Mitotic Cell ◽  
S Phase ◽  
Mitotic Cell Cycle ◽  
Meiotic Cell ◽  
Cyclin Dependent Kinases ◽  
Negative Factor

ABSTRACT The meiotic cell cycle is modified from the mitotic cell cycle by having a premeiotic S phase which leads to high levels of recombination, a reductional pattern of chromosome segregation at the first division, and a second division with no intervening DNA synthesis. Cyclin-dependent kinases are essential for progression through the meiotic cell cycle, as for the mitotic cycle. Here we show that a fission yeast cyclin, Rem1, is present only during meiosis. Cells lacking Rem1 have impaired meiotic recombination, and Rem1 is required for premeiotic DNA synthesis when Cig2 is not present. rem1 expression is regulated at the level of both transcription and splicing, with Mei4 as a positive and Cig2 a negative factor of rem1 splicing. This regulation ensures the timely appearance of the different cyclins during meiosis, which is required for the proper progression through the meiotic cell cycle. We propose that the meiosis-specific B-type cyclin Rem1 has a central role in bringing about progression through meiosis.

scholarly journals Differential requirements for DNA replication in the activation of mitotic checkpoints in Saccharomyces cerevisiae.

1997 ◽  
Vol 17 (6) ◽  
pp. 3315-3322 ◽  
Author(s):  
P A Tavormina ◽  
Y Wang ◽  
D J Burke
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Damage ◽  
Cell Division ◽  
Dna Replication ◽  
Gamma Irradiation ◽  
Chromosome Segregation ◽  
Mitotic Checkpoint ◽  
S Phase ◽  
Temperature Sensitive ◽  
Dna Metabolism

Checkpoints prevent inaccurate chromosome segregation by inhibiting cell division when errors in mitotic processes are encountered. We used a temperature-sensitive mutation, dbf4, to examine the requirement for DNA replication in establishing mitotic checkpoint arrest. We used gamma-irradiation to induce DNA damage and hydroxyurea to limit deoxyribonucleotides in cells deprived of DBF4 function to investigate the requirement for DNA replication in DNA-responsive checkpoints. In the absence of DNA replication, mitosis was not inhibited by these treatments, which normally activate the DNA damage and DNA replication checkpoints. Our results support a model that indicates that the assembly of replication structures is critical for cells to respond to defects in DNA metabolism. We show that activating the spindle checkpoint with nocodazole does not require prior progression through S phase but does require a stable kinetochore.

Chromosome segregation from cell hybrids.II. Do differences in parental cell growth rates and phase times determine direction of loss?

1986 ◽  
Vol 28 (5) ◽  
pp. 735-743 ◽  
Author(s):  
Jennifer A. Marshall Graves ◽  
Jaclyn M. Wrigley
Keyword(s):  
Cell Cycle ◽  
Chromosome Segregation ◽  
Chinese Hamster ◽  
Parental Cell ◽  
S Phase ◽  
Chromosome Loss ◽  
Parent Cell ◽  
Cycle Times ◽  
Cell Hybrids ◽  
The One

The hypothesis that the direction of chromosome segregation in cell hybrids is determined by the interaction of parent cell cycles, or S-phase times, predicts that the segregant parent will always be the one with the longer cycle, or the longer S phase, and that late replicating chromosomes will be more frequently lost. We have tested this hypothesis by studying cell cycle parameters of mouse, Chinese hamster, and platypus parent cells and by observing chromosome loss and replication patterns in hybrids between them. Two types of hybrids have been studied: mouse–hamster hybrids showed gradual segregation, in one or other direction, of 10–60% chromosomes, while rodent–platypus hybrids (which could be selected under conditions optimal for either parent cell) showed rapid and extreme segregation of platypus chromosomes. We found no correlation between the direction of segregation and the relative lengths of parental cycle times, or phase times, nor between sequence of replication and frequency with which segregant chromosomes are lost. We therefore conclude that the direction and extent of segregation is not directly determined by the interaction of parental cycle or phase times.Key words: cell hybrids, chromosome loss, cell cycle, S phase.

scholarly journals Anaphase Bridges: Not All Natural Fibers Are Healthy

Genes ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 902
Author(s):  
Alice Finardi ◽  
Lucia F. Massari ◽  
Rosella Visintin
Keyword(s):  
Chromosome Segregation ◽  
Sister Chromatid ◽  
Potential Role ◽  
Genome Instability ◽  
Natural Fibers ◽  
S Phase ◽  
Dna Lesions ◽  
Anaphase Bridges ◽  
Daughter Cells ◽  
Sister Chromatids

At each round of cell division, the DNA must be correctly duplicated and distributed between the two daughter cells to maintain genome identity. In order to achieve proper chromosome replication and segregation, sister chromatids must be recognized as such and kept together until their separation. This process of cohesion is mainly achieved through proteinaceous linkages of cohesin complexes, which are loaded on the sister chromatids as they are generated during S phase. Cohesion between sister chromatids must be fully removed at anaphase to allow chromosome segregation. Other (non-proteinaceous) sources of cohesion between sister chromatids consist of DNA linkages or sister chromatid intertwines. DNA linkages are a natural consequence of DNA replication, but must be timely resolved before chromosome segregation to avoid the arising of DNA lesions and genome instability, a hallmark of cancer development. As complete resolution of sister chromatid intertwines only occurs during chromosome segregation, it is not clear whether DNA linkages that persist in mitosis are simply an unwanted leftover or whether they have a functional role. In this review, we provide an overview of DNA linkages between sister chromatids, from their origin to their resolution, and we discuss the consequences of a failure in their detection and processing and speculate on their potential role.

scholarly journals Replication stress in early S phase generates apparent micronuclei and chromosome rearrangement in fission yeast

2015 ◽  
Vol 26 (19) ◽  
pp. 3439-3450 ◽  
Author(s):  
Sarah A. Sabatinos ◽  
Nimna S. Ranatunga ◽  
Ji-Ping Yuan ◽  
Marc D. Green ◽  
Susan L. Forsburg
Keyword(s):  
Fission Yeast ◽  
Chromosome Segregation ◽  
Chromosome Rearrangement ◽  
Chromosome Instability ◽  
Replication Stress ◽  
Parent Nucleus ◽  
S Phase ◽  
Yeast Mutant ◽  
Mcm Helicase ◽  
Dna Replication Stress

DNA replication stress causes genome mutations, rearrangements, and chromosome missegregation, which are implicated in cancer. We analyze a fission yeast mutant that is unable to complete S phase due to a defective subunit of the MCM helicase. Despite underreplicated and damaged DNA, these cells evade the G2 damage checkpoint to form ultrafine bridges, fragmented centromeres, and uneven chromosome segregations that resembles micronuclei. These micronuclei retain DNA damage markers and frequently rejoin with the parent nucleus. Surviving cells show an increased rate of mutation and chromosome rearrangement. This first report of micronucleus-like segregation in a yeast replication mutant establishes underreplication as an important factor contributing to checkpoint escape, abnormal chromosome segregation, and chromosome instability.

Sign in / Sign up

Export Citation Format

Share Document