Meiotic non-disjunction in germline immortality

Univ Of North Carolina Chapel Hill, Chapel Hill NC

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Abstract

Project Summary/Abstract Aging is a well-characterized process during which cells undergo an age-dependent decline in fitness and reproduction resulting in a finite lifespans. Even though many diseases are caused by premature aging of different cell populations, often in response to a stress, there are still many unknowns. The immortal germline in Caenorhabditis elegans has been shown to be a powerful model to better elucidate the stresses inducing aging and the cellular responses to stress. In certain genetic backgrounds, the germline of C. elegans will become mortal, meaning that after reproducing for many generations, sterility will occur. In most cases, loss of immortality has been found to be due to impaired genomic silencing or telomerase-mediated telomere maintenance in germ cells. In addition to these pathways, preliminary data suggests that proper chromosome segregation during meiosis is necessary for maintenance of germline immortality over multiple generations. We have identified a class of Mortal Germline mutants with non-disjunction events due to either disrupted Chromosome IV pairing or short telomeres. The long-term goal of this project is to investigate how meiotic processes protect the germline from accumulation of stress or damage over multiple generations. I propose to study 1) the pathway disrupted by loss of Chromosome IV pairing and 2) how short telomeres cause non- disjunction and their role in germline immortality. This project will provide insights into both the inherited stress causing loss of germline immortality and the role of telomere length in both germline immortality and meiotic processes. By studying both the importance of chromosome pairing and the role of telomere length in chromosome segregation, substantial advances can be made in understanding the biology underlying germline immortality.