All sexually reproducing organisms rely on meiosis to generate gametes, haploid cells containing one complete set of chromosomes. Central to this process is a reductional division, during which homologous chromosomes segregate to opposite spindle poles. Accurate segregation of chromosomes during meiosis is vital for the development of a fertilized embryo and for propagation of a species. To segregate faithfully away from its homologous partner, each chromosome must first find its proper partner, align with it along its entire length, and form a physical linkage through the act of meiotic crossing-over, or genetic exchange. Somehow meiotic chromosome interactions are governed to ensure that meiotic crossing-over occurs only between appropriate homologous partners, while inappropriate recombination events are prevented. In higher eukaryotes these interactions are clearly regulated at a level beyond mere sequence homology, since homologous sequences on nonhomologous chromosomes are normally precluded from synapsing and undergoing exchange. In C. elegans, chromosomes lacking special cis-acting sites known as """"""""Pairing Centers"""""""" fail to undergo crossing-over and segregate at random, probably because they are unable to synapse. Thus, the Pairing Centers play a major role in governing inter-homolog interactions during meiosis. Pairing Centers have been roughly mapped on each chromosome, but no detailed information about their function exists. Combining the molecular and cytological tools available in C. elegans, we will define and characterize the molecular components underlying the role of Pairing Centers in meiotic chromosome behavior. First, we will delimit the sequence components that give rise to Pairing Center function. Second, we will identify proteins that associate with the Pairing Center and characterize their roles in ensuring proper meiotic chromosome organization. Third, we will use cytological methods to determine the role of the Pairing Center in meiotic chromosome pairing and synapsis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM065591-01
Application #
6465302
Study Section
Genetics Study Section (GEN)
Program Officer
Carter, Anthony D
Project Start
2002-04-01
Project End
2007-03-31
Budget Start
2002-04-01
Budget End
2003-03-31
Support Year
1
Fiscal Year
2002
Total Cost
$299,138
Indirect Cost
Name
Lawrence Berkeley National Laboratory
Department
Biology
Type
Organized Research Units
DUNS #
078576738
City
Berkeley
State
CA
Country
United States
Zip Code
94720
Zhang, Liangyu; Köhler, Simone; Rillo-Bohn, Regina et al. (2018) A compartmentalized signaling network mediates crossover control in meiosis. Elife 7:
Rog, Ofer; Köhler, Simone; Dernburg, Abby F (2017) The synaptonemal complex has liquid crystalline properties and spatially regulates meiotic recombination factors. Elife 6:
Köhler, Simone; Wojcik, Michal; Xu, Ke et al. (2017) Superresolution microscopy reveals the three-dimensional organization of meiotic chromosome axes in intact Caenorhabditis elegans tissue. Proc Natl Acad Sci U S A 114:E4734-E4743
Yu, Zhouliang; Kim, Yumi; Dernburg, Abby F (2016) Meiotic recombination and the crossover assurance checkpoint in Caenorhabditis elegans. Semin Cell Dev Biol 54:106-16
Zhang, Liangyu; Ward, Jordan D; Cheng, Ze et al. (2015) The auxin-inducible degradation (AID) system enables versatile conditional protein depletion in C. elegans. Development 142:4374-84
Rog, Ofer; Dernburg, Abby F (2015) Direct Visualization Reveals Kinetics of Meiotic Chromosome Synapsis. Cell Rep :
Kim, Yumi; Kostow, Nora; Dernburg, Abby F (2015) The Chromosome Axis Mediates Feedback Control of CHK-2 to Ensure Crossover Formation in C. elegans. Dev Cell 35:247-61
Kim, Yumi; Rosenberg, Scott C; Kugel, Christine L et al. (2014) The chromosome axis controls meiotic events through a hierarchical assembly of HORMA domain proteins. Dev Cell 31:487-502
Rog, Ofer; Dernburg, Abby F (2013) Chromosome pairing and synapsis during Caenorhabditis elegans meiosis. Curr Opin Cell Biol 25:349-56
Stamper, Ericca L; Rodenbusch, Stacia E; Rosu, Simona et al. (2013) Identification of DSB-1, a protein required for initiation of meiotic recombination in Caenorhabditis elegans, illuminates a crossover assurance checkpoint. PLoS Genet 9:e1003679

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