Dr. Hong-Guo Yu
Ph.D., University of Georgia, 2000
Graduate Faculty Status
A postdoc position is available in the lab.
Our research goal is to understand how chromosomes organize themselves and segregate during cell division. In mitosis the cell replicates itself by equally partitioning duplicated chromosomes. In contrast, during the first division of meiosis, homologous chromosomes pair, recombine, then separate, but sister chromatids remain joined together until the second division of meiosis. Understanding the dynamics of chromosome organization and segregation during meiosis can provide insights into the causes of birth defects and aneuploidy. We use the budding yeast Saccharomyces cerevisiae as our experimental organism.
Mechanism of chromosome organization and genome integrity
We have found that condensin is required for the resolution of chromosome linkages that allow homologs to separate during meiosis. Recently, we developed a novel chromosome-tracking tool to determine meiotic chromosome dynamics in live cells (Figure 1) and showed that condensin-mediated chromosome organization coordinates replication, recombination and segregation of the repetitive rDNA sequences during yeast meiosis. We are currently focusing on the following research question: How do condensin and cohesin mediate chromosome organization at the site of a chromosome break to ensure accurate double-strand break processing and repair? Chromosome breakage is a hallmark of cancer cells. Investigating how errors in chromosome-break repair occur in a model eukaryote is essential to our understanding of chromosome metabolism in genomic instability in humans.
Figure 1. A chromosome-tracking system in budding yeast. (a) A flow chart showing the procedures for integration of 5xtetO. (b) Integration of 5xtetO confirmed by PCR. (C) rDNA morphology from fixed and live yeast cells. (D) Time-lapse microscopy showing dynamic movement of rDNA during meiosis. Bar, 5 μm.
Mechanism of centrosome duplication and separation during yeast meiosis
The yeast centrosome, also called the spindle-pole body (SPB), organizes microtubules required for a variety of cellular processes, including cell division. During meiosis, the centrosome is duplicated when chromosomes replicate. Duplicated centrosomes separate to form a bipolar spindle required for homolog separation during the first division of meiosis. Centrosomes duplicate again in the absence of DNA replication to establish two spindles for sister-chromatid separation in the second meiotic division. Coordination of centrosome duplication and separation with the two chromosome segregation cycles in meiosis is fundamental to maintaining genome integrity, but its mechanism remains unknown. We have revealed that the Aurora kinase Ipl1 in yeast is required for maintaining a close interaction between duplicated yeast SPBs, which we term SPB cohesion, analogous to sister-chromatid cohesion. Premature loss of SPB cohesion leads to SPB overduplication and the formation of multipolar spindles (Figure 2).
Figure 2. Centrosome (SPB) dynamics during yeast meiosis. Spc42 is marked by red fluorescent protein; αtubulin (Tub1) by green fluorescent protein. Note the tripolar spindle formation in the ipl1 mutant. WT, wild type. Bar, 2 μm.
The process of SPB reduplication during yeast meiosis provides an unparalleled experimental system in which to determine the molecular mechanism of centrosome duplication and its coordination with chromosome segregation during cell division.
Li, P., Y. Shao, H. Jin, and H.-G. Yu. 2015. Ndj1, a telomere-associated protein, regulates centrosome separation in budding yeast meiosis. Journal of Cell Biology 209:247-259. http://jcb.rupress.org/cgi/content/abstract/jcb.201408118
Jin, H., M. Avey, and H.-G. Yu. 2012. Is cohesin required for spindle-pole-body/centrosome cohesion? Communicative and Integrative Biology 5:26-29. (record in PubMed)
Jin, F.,H. Liu, P. Li, H.-G. Yu, and Y. Wang. 2012. Loss of function of the Cik1/Kar3 motor complex results in chromosomes with syntelic attachment that are sensed by the tension checkpoint. PLoS Genetics 8: e1002492. (record in PubMed)
Li, P., H. Jin, M. L. Hoang, and H.-G. Yu. 2011. Tracking chromosome dynamics in live yeast cells: coordinated movement of rDNA homologs and anaphase disassembly of the nucleolus during meiosis. Chromosome Research 19:1013-1026. (record in PubMed)
Shirk, K., H. Jin, T. H. Giddings, Jr., M. Winey, and H.-G. Yu. 2011. The Aurora kinase Ipl1 protects spindle pole body cohesion during yeast meiosis. Journal of Cell Science 124:2891-2896. (record in PubMed)
Lin, W., H. Jin, X. Liu, K. Hampton, and H.-G. Yu. 2011. Scc2 regulates gene expression by recruiting cohesin to the chromosome as a transcriptional activator during yeast meiosis. Molecular Biology of the Cell 22:1985-1996. (record in PubMed)
Lin, W., M. Wang, H. Jin, and H.-G. Yu. 2011. Cohesin plays a dual role in gene regulation and sister-chromatid cohesion during meiosis in Saccharomyces cerevisae. Genetics 187:1041-1051. (record in PubMed)
Brito, I. L., H.-G. Yu, and A. Amon. 2010. Condensins promote coorientation of sister chromatids during meiosis I in budding yeast. Genetics 185: 55-64. (record in PubMed)
Jin, H., V. Guacci, and H.-G. Yu. 2009. Pds5 is required for homologue pairing and inhibits synapsis of sister chromatids during yeast meiosis. Journal of Cell Biology 186: 713-725. (record in PubMed)
Macy, B., M. Wang, and H.-G. Yu. 2008. The many faces of shugoshin, the "guardian spirit," in chromosome segregation. Cell Cycle 8:1-3. (electronic version)
Yu, H.-G, and D. E. Koshland. 2007. The Aurora kinase Ipl1 maintains the centromeric localization of PP2A to protect cohesin during meiosis. Journal of Cell Biology 176: 911-918. (record in PubMed)
Yu, H.-G., and D. E. Koshland. 2005. Chromosome morphogenesis: condensin-dependent cohesin removal during meiosis. Cell 123:397-407. (record in PubMed)
Glynn, E. F., P. Megee, H.-G. Yu, C. Mistrot, E. Unal, D. E. Koshland, J. L. DeRisi, and J. L. Gerton. 2004. Genome-wide mapping of the cohesin complex in the yeast Saccharomyces cerevisiae. PLoS, Biology 2(9):1325-1339. (record in PubMed)
Yu, H.-G., and D. E. Koshland. 2003. Meiotic condensin is required for proper chromosome compaction, SC assembly, and resolution of recombination-dependent chromosome linkages. Journal of Cell Biology 163:937-947. (record in PubMed)Postdoctoral Associates: