scholarly journals DNA damage responses in mammalian oocytes

Reproduction ◽  
2016 ◽  
Vol 152 (1) ◽  
pp. R15-R22 ◽  
Author(s):  
Josie K Collins ◽  
Keith T Jones
Keyword(s):  
Dna Damage ◽  
Spindle Assembly Checkpoint ◽  
Germinal Vesicle ◽  
Spindle Assembly ◽  
Stages Of Growth ◽  
Microtubule Attachment ◽  
Dna Damage Responses ◽  
Chromosome Attachment ◽  
Spindle Microtubules ◽  
Meiosis I

DNA damage acquired during meiosis can lead to infertility and miscarriage. Hence, it should be important for an oocyte to be able to detect and respond to such events in order to make a healthy egg. Here, the strategies taken by oocytes during their stages of growth to respond to DNA damaging events are reviewed. In particular, recent evidence of a novel pathway in fully grown oocytes helps prevent the formation of mature eggs with DNA damage. It has been found that fully grown germinal vesicle stage oocytes that have been DNA damaged do not arrest at this point in meiosis, but instead undergo meiotic resumption and stall during the first meiotic division. The Spindle Assembly Checkpoint, which is a well-known mitotic pathway employed by somatic cells to monitor chromosome attachment to spindle microtubules, appears to be utilised by oocytes also to respond to DNA damage. As such maturing oocytes are arrested at metaphase I due to an active Spindle Assembly Checkpoint. This is surprising given this checkpoint has been previously studied in oocytes and considered to be weak and ineffectual because of its poor ability to be activated in response to microtubule attachment errors. Therefore, the involvement of the Spindle Assembly Checkpoint in DNA damage responses of mature oocytes during meiosis I uncovers a novel second function for this ubiquitous cellular checkpoint.

Evidence that the spindle assembly checkpoint does not regulate APCFzy activity in Drosophila female meiosis

Genome ◽  
2012 ◽  
Vol 55 (1) ◽  
pp. 63-67 ◽  
Author(s):  
Osamah Batiha ◽  
Andrew Swan
Keyword(s):  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Cyclin B ◽  
Meiotic Spindle ◽  
Loss Of Function ◽  
Female Meiosis ◽  
Chromosome Attachment ◽  
Spindle Microtubules ◽  
Made In

The spindle assembly checkpoint (SAC) plays an important role in mitotic cells to sense improper chromosome attachment to spindle microtubules and to inhibit APCFzy-dependent destruction of cyclin B and Securin; consequent initiation of anaphase until correct attachments are made. In Drosophila , SAC genes have been found to play a role in ensuring proper chromosome segregation in meiosis, possibly reflecting a similar role for the SAC in APCFzy inhibition during meiosis. We found that loss of function mutations in SAC genes, Mad2, zwilch, and mps1, do not lead to the predicted rise in APCFzy-dependent degradation of cyclin B either globally throughout the egg or locally on the meiotic spindle. Further, the SAC is not responsible for the inability of APCFzy to target cyclin B and promote anaphase in metaphase II arrested eggs from cort mutant females. Our findings support the argument that SAC proteins play checkpoint independent roles in Drosophila female meiosis and that other mechanisms must function to control APC activity.

scholarly journals Chromosome biorientation and APC activity remain uncoupled in oocytes with reduced volume

2017 ◽  
Vol 216 (12) ◽  
pp. 3949-3957 ◽  
Author(s):  
Simon I.R. Lane ◽  
Keith T. Jones
Keyword(s):  
Cell Volume ◽  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Anaphase Promoting Complex ◽  
Chromosome Missegregation ◽  
Anaphase Onset ◽  
Reduced Volume ◽  
Chromosome Attachment ◽  
Meiosis I

The spindle assembly checkpoint (SAC) prevents chromosome missegregation by coupling anaphase onset with correct chromosome attachment and tension to microtubules. It does this by generating a diffusible signal from free kinetochores into the cytoplasm, inhibiting the anaphase-promoting complex (APC). The volume in which this signal remains effective is unknown. This raises the possibility that cell volume may be the reason the SAC is weak, and chromosome segregation error-prone, in mammalian oocytes. Here, by a process of serial bisection, we analyzed the influence of oocyte volume on the ability of the SAC to inhibit bivalent segregation in meiosis I. We were able to generate oocytes with cytoplasmic volumes reduced by 86% and observed changes in APC activity consistent with increased SAC control. However, bivalent biorientation remained uncoupled from APC activity, leading to error-prone chromosome segregation. We conclude that volume is one factor contributing to SAC weakness in oocytes. However, additional factors likely uncouple chromosome biorientation with APC activity.

scholarly journals Spindle assembly checkpoint-related meiotic defect in oocytes from LT/Sv mice has cytoplasmic origin and diminishes in older females

Reproduction ◽  
2012 ◽  
Vol 144 (3) ◽  
pp. 331-338 ◽  
Author(s):  
Steffen Hoffmann ◽  
Marzena Król ◽  
Zbigniew Polanski
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Germinal Vesicle ◽  
Spindle Assembly ◽  
Cyclin B1 ◽  
Meiotic Metaphase ◽  
Wild Type ◽  
Anaphase Onset ◽  
Spindle Microtubules ◽  
Old Mice ◽  
Segregation Of Chromosomes

The spindle assembly checkpoint (SAC) ensures proper segregation of chromosomes by delaying anaphase onset until all kinetochores are properly attached to the spindle microtubules. Oocytes from the mouse strain LT/Sv arrest at the first meiotic metaphase (MI) due to, as reported recently, enormously prolonged activity of the SAC. We compared the dynamics of cyclin B1–GFP degradation, the process which is a measure of the SAC activity, in chromosomal and achromosomal halves of LT/Sv oocytes. In chromosome-containing oocyte halves arrested at MI, cyclin B1–GFP was not degraded indicating active SAC. However, in the halves lacking chromosomes, which is a condition precluding the SAC function, degradation always occurred confirming that MI arrest in LT/Sv oocytes is SAC dependent. Transferring the germinal vesicle (GV) from LT/Sv oocytes into the enucleated oocytes from wild-type mice resulted in the progression through meiosis one, indicating that a SAC-activating defect in LT/Sv oocytes is cytoplasmic, yet can be rescued by foreign cytoplasm. These results may help to define the etiology of the human infertility related to the oocyte MI arrest, indicating the involvement of the SAC as likely candidate, and point to GV transfer as the possible therapy. Finally, we found that majority of oocytes isolated from old LT/Sv mice complete the first meiosis. Reciprocal transfers of the GV between the oocytes from young and old LT/Sv females suggest that the factor(s) responsible for the reversal of the phenotype in oocytes from old mice is located both in the GV and in the cytoplasm.

scholarly journals Mps1 regulates spindle morphology through MCRS1 to promote chromosome alignment

2019 ◽  
Vol 30 (9) ◽  
pp. 1060-1068 ◽  
Author(s):  
Hongdan Yang ◽  
Fengxia Zhang ◽  
Ching-Jung Huang ◽  
Jun Liao ◽  
Ying Han ◽  
...  
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Underlying Mechanism ◽  
Genome Maintenance ◽  
Microtubule Attachment ◽  
Downstream Effectors ◽  
Chromosome Alignment ◽  
Assembly Factor ◽  
Spindle Microtubules

Accurate partitioning of chromosomes during mitosis is essential for genetic stability and requires the assembly of the dynamic mitotic spindle and proper kinetochore–microtubule attachment. The spindle assembly checkpoint (SAC) monitors the incompleteness and errors in kinetochore–microtubule attachment and delays anaphase. The SAC kinase Mps1 regulates the recruitment of downstream effectors to unattached kinetochores. Mps1 also actively promotes chromosome alignment during metaphase, but the underlying mechanism is not completely understood. Here, we show that Mps1 regulates chromosome alignment through MCRS1, a spindle assembly factor that controls the dynamics of the minus end of kinetochore microtubules. Mps1 binds and phosphorylates MCRS1. This mechanism enables KIF2A localization to the minus end of spindle microtubules. Thus, our study reveals a novel role of Mps1 in regulating the dynamics of the minus end of microtubules and expands the functions of Mps1 in genome maintenance.

scholarly journals OLA1 is responsible for normal spindle assembly and SAC activation in mouse oocytes

2019 ◽  
Author(s):  
Di Xie ◽  
Juan Zhang ◽  
JinLi Ding ◽  
Jing Yang ◽  
Yan Zhang
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Polar Body ◽  
Germinal Vesicle ◽  
Spindle Assembly ◽  
Mouse Oocyte ◽  
Immunofluorescent Staining ◽  
Germinal Vesicle Breakdown ◽  
Oocyte Meiosis ◽  
Polar Body Extrusion ◽  
Spread Analysis

Background. OLA1 is a member of the GTPase protein family, unlike other members, it can bind and hydrolyze ATP more efficiently than GTP. OLA1 participates in cell proliferation, oxidative response and tumorigenesis. However, whether OLA1 is also required for oocyte meiosis is still unknown. Methods. In this study, the localization, expression, and functions of OLA1 in the mouse oocyte meiosis were examined. Immunofluorescent and confocal microscopy were used to explore the location pattern of OLA1 in the mouse oocyte. Moreover, nocodazole treatment was used to confirm the spindle-like location of OLA1 during mouse meiosis. Western blot was used to explore the expression pattern of OLA1 in the mouse oocyte. Microinjection of siRNA was used to explore the OLA1 functions in the mouse oocyte meiosis. In addition, chromosome spreading was used to investigate the spindle assembly checkpoint (SAC) activity. Results. Immunofluorescent staining showed that OLA1 evenly distributed in the cytoplasm at germinal vesicle (GV) stage. After meiosis resumption (GVBD), OLA1 co-localized with spindles, which was further identified by nocodazole treatment experiments. Knockdown of OLA1 impaired the germinal vesicle breakdown progression and finally resulted in a lower polar body extrusion rate. Immunofluorescence analysis indicated that knockdown of OLA1 led to abnormal spindle assembly, which was evidenced by multipolar spindles in OLA1-RNAi-oocytes. After 6 h post-GVBD in culture, an increased proportion of oocyte which has precociously entered into anaphase/telephase I (A/TI) was observed in OLA1-knockdown oocytes, suggesting that loss of OLA1 resulted in the premature segregation of homologous chromosomes. In addition, the chromosome spread analysis suggested that OLA1 knockdown induced premature anaphase onset was due to the precocious inactivation of SAC. Taken together, we concluded that OLA1 plays important role in GVBD, spindle assembly and SAC activation maintenance in oocyte meiosis.

scholarly journals DNA damage induces a meiotic arrest in mouse oocytes mediated by the spindle assembly checkpoint

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Josie K. Collins ◽  
Simon I. R. Lane ◽  
Julie A. Merriman ◽  
Keith T. Jones
Keyword(s):  
Dna Damage ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Meiotic Arrest ◽  
Mouse Oocytes

scholarly journals Restaging the Spindle Assembly Checkpoint in Female Mammalian Meiosis I

Cell Cycle ◽  
2005 ◽  
Vol 4 (5) ◽  
pp. 650-653 ◽  
Author(s):  
Hayden A. Homer ◽  
Alex McDougal ◽  
Mark Levasseur ◽  
Mary Herbert
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Meiosis I
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