Reference Report

Reference
Citation	Laurencon, A., Purdy, A., Sekelsky, J., Hawley, R.S., Su, T.T. (2003). Phenotypic analysis of separation-of-function alleles of MEI-41, Drosophila ATM/ATR. Genetics 164(2): 589--601. (Export to RIS)
FlyBase ID	FBrf0160718
Publication Type	Research paper
PubMed ID	12807779
PubMed Abstract	ATM/ATR kinases act as signal transducers in eukaryotic DNA damage and replication checkpoints. Mutations in ATM/ATR homologs have pleiotropic effects that range from sterility to increased killing by genotoxins in humans, mice, and Drosophila. Here we report the generation of a null allele of mei-41, Drosophila ATM/ATR homolog, and the use of it to document a semidominant effect on a larval mitotic checkpoint and methyl methanesulfonate (MMS) sensitivity. We also tested the role of mei-41 in a recently characterized checkpoint that delays metaphase/anaphase transition after DNA damage in cellular embryos. We then compare five existing mei-41 alleles to the null with respect to known phenotypes (female sterility, cell cycle checkpoints, and MMS resistance). We find that not all phenotypes are affected equally by each allele, i.e., the functions of MEI-41 in ensuring fertility, cell cycle regulation, and resistance to genotoxins are genetically separable. We propose that MEI-41 acts not in a single rigid signal transduction pathway, but in multiple molecular contexts to carry out its many functions. Sequence analysis identified mutations, which, for most alleles, fall in the poorly characterized region outside the kinase domain; this allowed us to tentatively identify additional functional domains of MEI-41 that could be subjected to future structure-function studies of this key molecule.
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Genetics
Title	Genetics
Publication Year	1916-
ISBN/ISSN	0016-6731
Data from Reference
Aberrations (3)
	Df(1)19 Df(1)78B Dp(1;4)r⁺l
Alleles (40)
	Gpi1² l(1)14Cc^XR44 l(1)14Cd^11b-8 l(1)14Ce^4a-47 mei-41^12-1483 mei-41^12-3616 mei-41^29D mei-41^99B mei-41^A1 mei-41^A7 mei-41^A8 mei-41^A9 mei-41^A10 mei-41^A11 mei-41^A12 mei-41^A15 mei-41^A16 mei-41^A22 mei-41^A27 mei-41^A28 mei-41^A29 mei-41^D1 mei-41^D2 mei-41^D3 mei-41^D4 mei-41^D5 mei-41^D7 mei-41^D8 mei-41^D9 mei-41^D10 mei-41^D11 mei-41^D12 mei-41^D13 mei-41^D14 mei-41^D15 mei-41^D18 mei-41^D19 mei-41^RT1 mei-41^RT2 U2af50^XR18
Genes (8)
	Gpi1 His3 l(1)14Cc l(1)14Cd l(1)14Ce mei-41 tefu U2af50
Insertions (2)
	P{5'3'}mei-41^99B P{}mei-41^RT1