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Title: Roles of SPD-3 during C. elegans meiosis
Author: Labrador Gonzalez, Leticia
ISNI:       0000 0004 2718 8365
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2012
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Correct chromosome segregation during meiosis requires that the paternal and maternal copies of each chromosome, known as homologues, recognise and pair with one another before they can undergo meiotic recombination. Defects in this process lead to sterility and the formation of aneuploid gametes, which is the leading cause of birth defects in humans. In this study the process of homologue pairing during meiosis has been investigated in C. elegans, an organism especially well suited for meiotic studies. During a genetic screen for meiotic mutants, several mutants with defects in meiotic chromosome segregation were isolated. One of these mutants, me85, was identified as a new allele of the spd-3 gene, which had previously been shown to be required for mitotic divisions in the early embryo. spd-3(me85) mutants display defects in homologue pairing similar to those observed in mutants lacking SUN-1 or ZYG-12, two proteins that form a bridge across the nuclear envelope (NE). This bridge transmits cytoskeletal forces generated outside the nucleus to meiotic chromosomes inside the nucleus, thereby facilitating chromosome clustering, a process that is though to facilitate homology search. The localisation of SUN-1 and ZYG-12 to the NE is not affected in spd-3(me85) mutants and chromosomes remain tethered to the NE. However, live imaging experiments in spd-3(me85) mutants demonstrate that the movement of chromosomes through the NE is severely impaired, which results in lack of chromosome clustering. Knocking down the activity of the dynein-dynactin complex by RNAi resulted in a phenocopy of the chromosome clustering defects observed in spd-3(me85) mutants, although dynein localisation is not affected in spd-3(me85) mutants. Interestingly, the SPD-3 protein localizes outside the nucleus in the germline. These observations suggest that SPD-3 affects the earliest steps of homologue pairing by regulating the cytoskeletal forces outside the nucleus.
Supervisor: Martinez-Perez, Enrique Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral