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Control of meiosis and oocyte development by DNA damage checkpoints in Drosophila melanogaster

Objective

DNA damage response (DDR) monitors chromosome status to ensure correct homologous recombination, genomic integrity and chromosome segregation. Thus the effect of DDR activation upon exogenous DNA breaks has been intensely studied. Less is known about the effects of such mechanisms due to endogenous breaks. In multicellular organisms meiosis is a classical example of double strand break (DSB) production and repair occurring concomitantly with gamete development. In Drosophila persistent meiotic DSBs activates the ATR/Mei-41 checkpoint, delays progression through meiosis and causes defects in DNA condensation in the oocyte nucleus. Checkpoint activation has also been linked to decreased levels of the TGFα-like molecule Gurken (GRK), which controls normal eggshell patterning. I used this easy scorable eggshell phenotype in a germ line mosaic screen to identify new genes affecting meiotic progression, DNA condensation and GRK signalling. My work on these mutants challenged the hypothesis that checkpoint activation upon persistent DSBs is exclusively mediated by ATR kinase and instead reveals a more complex network of interactions that link DSB formation, checkpoint activation, meiotic delay, DNA condensation and GRK synthesis. To understand how multicellular organisms monitor chromatin integrity during meiosis and how these surveillance mechanisms affect development I propose the study of the cohesion gene dPds5 in early and late meiosis, the characterization of two rasiRNA genes montecristo and sancho-panza in transposon silencing during oogenesis and the identification of genes downstream of checkpoint pathway mediating eggshell polarity response upon checkpoint activation. I discuss two major new ideas explored in this project: 1. cohesion is required for eggshell polarity, and 2. various branches of the DDR monitor aspects of chromatin independently of DSB.

Field of science

  • /natural sciences/biological sciences/genetics and heredity/chromosome
  • /natural sciences/biological sciences/genetics and heredity/heredity

Call for proposal

FP7-PEOPLE-IRG-2008
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Funding Scheme

MC-IRG - International Re-integration Grants (IRG)
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Coordinator

FUNDACAO CALOUSTE GULBENKIAN
Address
Avenida Berna 45
1000 Lisboa
Portugal
Activity type
Research Organisations
EU contribution
€ 100 000
Administrative Contact
José Mário Leite (Dr.)