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MEI-41, MUS304, GRP, and OKR

ATM and ATR are protein kinases that play key roles in the response to DNA damage. [Note: you'll often hear people say they are PI3 kinases. They are not. PI3 is a lipid, but ATM and ATR phosphorylate proteins.] The best understood function of ATM and ATR is in regulating the cell cycle in response the DNA damage. In vertebrates, these DNA damage-dependent checkpoint functions are split between ATM and ATR. In Drosophila, however, the ATR ortholog MEI-41 carries most checkpoint responsiblity. MUS304 is a non-catalytic protein partner of MEI-41, orthologous to ATRIP. Two of the major targets of ATM and ATR are CHK1 and CHK2; the Drosophila orthologs of these are encoded by grapes (grp) and loki (lok).

Vertebrate: ATR ATRIP CHK1 CHK2
Drosophila:     MEI-41        MUS304        GRP        LOK   

MEI-41, GRP, and LOK in DSB repair

mei-41 mutants are extremely hypersensitive to many types of DNA damaging agents, including ionizing radiation. Some or all of this hypersensitivity may be due to failure to establish cell cycle checkpoints in these mutants. However, it is also possible that the MEI-41 protein has additional roles in the DNA damage response, such as a direct role in DNA repair. We measured this with a repair assay we developed, but found an unexpectedly mild phenotype. Our results suggested that MEI-41 is required only late the SDSA pathway. Furthermore, we found that this function is partially independent of the two known transducers of the checkpoint signal, GRP and LOK. For more, see  

J. LaRocque, B. Jaklevic, T.T. Su, and J. Sekelsky (2007) Drosophila ATR in double-strand break repair. Genetics 175: 1023-1033.

MEI-41, GRP, and LOK in responding to spontaneous damage

Mutants that lack MEI-41, MUS304, GRP, or LOK are perfectly viable (for all but lok, mutant females are sterile due to a requirement in early embryonic development). However, if the dosage of DNA polymerase alpha is reduced, several developmental defects are observed. For more, see our DNA-Pol alpha page and

J. LaRocque, D.L. Dougherty, S. Hussain, and J. Sekelsky (2007) Reducing DNA polymerase &alpha in the absence of Drosophila ATR leads to P53-dependent apoptosis and developmental defects. Genetics 176: 1441-1451.

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