Aurora B Kinase A Key to Understanding Human Reproduction
Professor Juan Jimenez's team found in fission yeast that Aurora B kinase resets chromosome-microtubule attachments between the two meiotic divisions, ensuring sister chromatids separate correctly.
How cells divide and create new life is a mystery that has long fascinated scientists. In the center of this process is a structure called the spindle, which is crucial in sorting and moving chromosomes into new cells. Think of it as a cellular machine that ensures each new cell receives the correct set of genetic instructions. This machine operates through thread-like structures known as microtubules, which come in two types, each with a unique role in moving and positioning chromosomes. At the core of this operation are kinetochores, complex protein structures that attach chromosomes to these microtubules. Especially in meiosis, a unique form of cell division crucial for sexual reproduction, understanding the interplay of these components is critical. Meiosis involves two rounds of chromosome sorting after a single DNA replication, leading to the formation of haploid gametes, or sex cells. This study delves into the mechanics of how these components work together during the transition from the first to the second round of meiosis, a process fundamental to cellular biology yet not fully understood.
In a groundbreaking discovery led by Professor Juan Jimenez, and his team Sergio Villa-Consuegra and Professor Víctor Tallada from the Universidad Pablo de Olavide, the critical role of a protein called Aurora B kinase in meiosis has been unveiled. This protein plays a central role in meiosis, the process of cell division that is crucial for sexual reproduction. Their research, published in the journal iScience, uses fission yeasts as a model organism and provides profound insights into the complexities of meiotic division.
Professor Jimenez explains, “During meiosis, to ensure the accurate distribution of genetic material, it is crucial that certain structures within the cell, known as spindle microtubule-kinetochore arrays, behave in specific ways. In the first round of meiosis (MI), they need to align homologous chromosomes, but in the second round (MII), they need to separate sister chromatids.” This distinction is vital for accurate genetic distribution to the resulting gametes.
The study focuses on Aurora B kinase, a key protein previously known for its role in standard cell division, or mitosis. “We discovered that the repositioning of this protein to different parts of the cell becomes essential to reset these structures from the first to the second round of meiosis, satisfying what is known as the spindle assembly checkpoint (SAC) and generating the proper arrangements for the second round of division,” says Professor Jimenez. This repositioning is crucial to prevent errors in the distribution of chromosomes during meiosis II, which can lead to birth defects and infertility in humans.
The research team employed a variety of sophisticated techniques to uncover the critical role of Aurora B kinase in meiosis. They used specific inhibitors in Aurora B kinase inhibition assays to understand the functional role of this protein in the meiotic process. Additionally, live-cell microscopy allowed the researchers to observe and record the dynamic processes occurring within living cells in real time. This was particularly crucial for studying the behavior and interaction of chromosomes and spindle fibers during cell division. Lastly, the team performed detailed image analysis and measurement of spindle and chromosome dynamics. This involved capturing and analyzing high-resolution images to quantify changes in spindle structures and chromosome movements, providing a comprehensive understanding of the meiotic process at a molecular level.
The research further reveals the critical function of a protein known as Imp1 in this process. “In cells lacking sufficient amounts of this protein, we observed the simultaneous assembly of structures from the first and second rounds of meiosis, leading to cells with both structures coexisting. This unusual scenario results in errors during the second round of meiosis, emphasizing the importance of timely dynamics of these cellular structures,” highlights Professor Jimenez.
Professor Jimenez elaborates on the precision required in these cellular processes, “The delay induced by the SAC allows cells enough time to correct any improper attachments, ensuring accurate chromosome distribution during standard cell division.”
One of the study’s most significant findings is the role of a complex involving Aurora B in restoring normal chromosome distribution. “The release of this complex from a specific area in the cell during the transition between the two rounds of meiosis is a key step. It allows the cell to reset the arrangements at kinetochores, essential for assembling the correct structures for chromosome distribution and proper SAC function at the onset of the second round,” explains Professor Jimenez. This discovery highlights the complex interplay of cellular components during meiosis.
In summary, this study not only enriches our understanding of meiosis but also opens new avenues for addressing genetic disorders resulting from meiotic errors.
About the researcher
Dr. Juan Jimenez
Dr. Juan Jimenez is a Full Professor of Genetics at the Universidad Pablo de Olavide (UPO) and PI of the CABD research institute, Seville, Spain. He obtained a PhD in Genetics from the Laboratory of Dr.… Tahia Benítez, University of Seville, Spain in 1987, with a period of research at the Gulbenkian Science Institute supervised by Prof. N. van Uden. During this period, he was an assistant professor in the Department of Genetics, obtained a UNESCO scholarship and received the Seville City Council Award. In 1987 he began a postdoctoral period at the ICRF in London and at the Microbiology Unit of the University of Oxford, UK, in Dr. Paul Nurse's Lab (Nobel Prize 2001), closely collaborating with Dr. David Glover (University of Dundee, UK) to identify master genes regulating the cell cycle during fly development. He received the Cephalosporin Junior Research Fellowship at Linacre College. In 1989 he returned to Spain as Professor at the Faculty of Sciences of the University of Malaga. In 2000 he moved to the UPO, where he was Vice-President for Research and President of the University. During the Vice-Presidency period he co-founded the CABD institute (joint CSIC-UPO research center) and was the first director of this center. During 2012 he was a research visitor at the Department of Biochemistry (Juan Mata's Lab) at the University of Cambridge, UK. His research has mainly focused on how different cellular functions such as translation, cytokinesis or spindle disassembly are coordinated with mechanisms that regulate the mitotic and meiotic cell cycle. Applied research on the formation of biofilms by “flor wine yeasts” and the development of algorithms for the in silico search for small ORFs (AnABlast) are also research topics of his group (Orcid: https://orcid.org/0000 -0002-3851-7393).
Journal reference
Sergio Villa-Consuegra, Víctor A. Tallada, Juan Jimenez, “Aurora B kinase erases monopolar microtubule-kinetochore arrays at the meiosis I-II transition,” iScience, 2023. DOI: https://doi.org/10.1016/j.isci.2023.108339.
