Chromosome separation is a basic biological process in which chromosomes are evenly distributed to two daughter cells during cell division. It is also an important mechanism to maintain genome stability and correctly transmit genetic information. Any mistake in this process will lead to aneuploidy, which can induce cancer in somatic cells. In female germ cells, aneuploidy egg formation is promoted, which is one of the important reasons for female infertility and birth defects.
The precise separation of chromosomes depends on the dynamic regulation of cohesin and its regulatory factors. In the process of mitosis, a large number of cohesin is dissociated from the chromosomal arm in prophase by its release factor Wapl, and then a small amount of cohesin in the centromere region is cut by protease separation to metaphase, so as to start chromosome separation [1,2]. However, meiosis occurs in mammalian female germ cells, with DNA replication once, but cell division twice (first meiosis and second meiosis). The first meiosis is very different from the mitosis, which occurs homologous chromosome separation. The cohesin on the chromosome arm is cut off by the separation in the metaphase and separated from the chromosome [3]. The releasing factor Wapl does not participate in this process. Therefore, it is still unclear what function Wapl plays in the first meiosis of mammalian oocytes and its regulatory mechanism. On April 8, 2020, the xiongbo research group of School of animal science and technology of Nanjing Agricultural University published a research paper entitled "the cohesin release factor Wapl interactions with Bub3 to government sac activity in male dimension I" in the Journal of science advances. This study revealed that Wapl, a chromosomal adhesin releasing factor, is involved in the regulation of the activity of spindle assembly checkpoint in the first meiosis of oocytes through its interaction with Bub3. In order to study the role of Wapl in the process of oocyte meiosis, the researchers observed two important events in the process of oocyte development and maturation: germinal vesicle rupture (GVBD), i.e. meiosis recovery, and first polar body expulsion (PB1), i.e. oocyte maturation. Unexpectedly, the loss of Wapl did not affect the rupture of raw foam and the final discharge of the first polar body, but resulted in the early discharge of the first polar body at the 6th and 7th hours after the rupture of raw foam. This suggests that Wapl deletion accelerates meiotic maturation and suggests that Wapl deletion may lead to the inactivation of spindle assembly checkpoint (Fig. 1). Figure 1: Wapl deletion accelerates the meiosis process of oocytes further. The researchers screened and confirmed the interaction between Wapl and a classic spindle assembly checkpoint protein Bub3 by immunoprecipitation and mass spectrometry, and then speculated that Wapl may affect the spindle assembly checkpoint activity through Bub3. Subsequently, the researchers examined the location and protein level of Bub3 in Wapl deficient oocytes. The results showed that the loss of Wapl resulted in the loss of the location of Bub3 on the kinetochore and the decrease of Bub3 protein. In Wapl deficient oocytes, the expression of exogenous Wapl restored them to near normal protein level, and the localization and protein content of Bub3 were significantly restored, indicating that Bub3 was indeed the downstream effector molecule of Wapl (Fig. 2). Figure 2: the spindle assembly test point of Wapl and Bub3 interaction regulation. In addition, the researchers also expressed exogenous Bub3 in Wapl deficient oocytes to observe whether the phenotype defects caused by Wapl deletion can be recovered. The results showed that the expression of Bub3 can restore the meiosis process to normal level, and also can restore the aneuploidy caused by the spindle assembly and chromosome arrangement abnormality caused by Wapl deletion (Fig. 3). Figure 3: expression of Bub3 can save the meiosis defects caused by Wapl deletion. In conclusion, this study clarifies the new function of chromosome binding protein Wapl as a spindle assembly checkpoint in meiosis by means of molecular biology, cell biology and biochemistry, and expands the cognition of the biological process involved in chromosome binding protein, which is the two cell cycle The relationship between regulatory networks (chromosomal binding protein and spindle assembly checkpoint) provides direct evidence, and also provides new ideas and theoretical basis for the study of the causes of aneuploid oogenesis in humans and animals. Zhou Changyin, a doctoral student of Nanjing Agricultural University, is the first author of this paper, and Professor Xiong Bo is the corresponding author. Paper link:
Https://advances.sciencemag.org/content/6/15/eaax3969 reference 1. Hauf s, Waizenegger IC and Peters JM. Cohesin clearance by separate required for anaphase and cytokinesis in human cells. Science. 2001; 293 (5533): 1320-1323.2, Kueng s, hegemann B, Peters BH, Lipp JJ, schleiffer a, Mechtler K and Peters JM. Wapl controls the dynamic association of cohesin with chromatin. Cell. 2006; 127(5):955-967.3、Herbert M, Levasseur M, Homer H, Yallop K, Murdoch A and McDougall A. Homologue disjunction in mouse oocytes requires proteolysis of securin and cyclin B1. Nature cell biology. 2003; 5(11):1023-1025.
BioWorld BioWorld has always been committed to reporting the most cutting-edge, important and interesting research progress in the field of life science. At present, 300000 scholars have paid attention to the whole network. Now, a communication group in the field of life science / medicine / science popularization is established. To enter the group, please long press the QR code below to add the administrator wechat.
Warm tip: Please note (name / school / major / position) when adding administrator wechat so that we can invite you to the corresponding communication group.
Click to see, pass on your taste