Faithin Omaha eBook Collection

Download or read book Control of Interactions Between Homologous Chromosomes During Meiosis written by Neeraj Joshi and published by . This book was released on 2014 with total page 240 pages. Available in PDF, EPUB and Kindle. Book excerpt: In sexually reproducing organisms, haploid gametes arise from diploid germ cells through the specialized cell division of meiosis. Unique features of meiosis include programmed double strand break (DSB) formation, preferential DSB repair with the homologous chromosome (homolog), synapsis and crossover (CO) formation. Without COs, homologs mis-segregate, resulting in aneuploid gametes which exhibit a chromosome surplus or deficit. Aneuploidy is often associated with birth defects and cancer. Here, I have used budding yeast as a model organism to investigate: (i) how recombination at the DNA level is linked to transitions in chromosome structure, (ii) how preferential use of the homolog versus the sister chromatid for repair of meiotic DSBs is established, and (iii) how global DSB levels affect meiotic cell cycle progression. I have also developed the Homolog Pairing Capture (HPC) assay, a novel method for identifying pairing regions between homologous chromosomes. My work demonstrates that the meiosis-specific AAA ATPase Pch2 links chromosome morphogenesis with recombination at the DNA level thereby shaping the genome-wide recombination landscape (Joshi et al. 2009). I have discovered that two meiotic DSBs subsets, "earlier, low abundance" and "later, high abundance" DSBs exhibit distinct features (Joshi and Börner, submitted). Early, low level DSBs lack homolog bias. Their repair is controlled by universally conserved checkpoint kinase Tel1/ATM as well as by meiosis-specific checkpoint ATPase Pch2. Processing of "later, high abundance" DSBs is primarily controlled by checkpoint kinase Mec1/ATR. These findings identify unique roles for presumed checkpoint factors in wild-type meiosis. I have further discovered a role of nucleus-wide abundance of DSBs in activation of the meiotic recombination checkpoint. Shared features of normal meiosis at elevated temperatures and defective meiosis identifies novel roles of the recombination checkpoint during wild-type meiosis. Together, these findings suggest that meiotic checkpoint components orchestrate events at three levels, namely, chromosome structure, DNA recombination, and cell-cycle progression, thereby ensuring accurate segregation of homologous chromosomes.