Drosophila homologue of the Rothmund–Thomson syndrome gene: Essential function in DNA replication during development

Members of the RecQ family play critical roles in maintaining genome integrity. Mutations in human RecQL4 cause a rare genetic disorder, Rothmund–Thomson syndrome. Transgenic mice experiments showed that the RecQ4 null mutant causes embryonic lethality. Although biochemical evidence suggests that th...

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Bibliographic Details
Published in:Developmental biology 2008-11, Vol.323 (1), p.130-142
Main Authors: Wu, Jianhong, Capp, Christopher, Feng, Liping, Hsieh, Tao-shih
Format: Article
Language:English
Subjects:
Animals
DNA replication
DNA Replication - genetics
Drosophila
Drosophila - embryology
Drosophila - genetics
Drosophila - physiology
Drosophila Proteins - genetics
Drosophila Proteins - metabolism
Drosophila Proteins - physiology
Embryo, Nonmammalian
Genes, Insect
Humans
Mutation
RecQ4
Rothmund-Thomson Syndrome - genetics
Rothmund-Thomson Syndrome - metabolism
Rothmund–Thomson syndrome
S Phase
Xenopus
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Summary:Members of the RecQ family play critical roles in maintaining genome integrity. Mutations in human RecQL4 cause a rare genetic disorder, Rothmund–Thomson syndrome. Transgenic mice experiments showed that the RecQ4 null mutant causes embryonic lethality. Although biochemical evidence suggests that the Xenopus RecQ4 is required for the initiation of DNA replication in the oocyte extract, its biological functions during development remain to be elucidated. We present here our results in establishing the use of Drosophila as a model system to probe RecQ4 functions. Immunofluorescence experiments monitoring the cellular distribution of RecQ4 demonstrated that RecQ4 expression peaks during S phase, and RecQ4 is expressed only in tissues active in DNA replication, but not in quiescent cells. We have isolated Drosophila RecQ4 hypomorphic mutants, recqEP and recq423, which specifically reduce chorion gene amplification of follicle cells by 4–5 fold, resulting in thin and fragile eggshells, and female sterility. Quantitative analysis on amplification defects over a 14-kb domain in chorion gene cluster suggests that RecQ4 may have a specific function at or near the origin of replication. A null allele recq419 causes a failure in cell proliferation, decrease in DNA replication, chromosomal fragmentation, and lethality at the stage of first instar larvae. The mosaic analysis indicates that cell clones with homozygous recq419 fail to proliferate. These results indicate that RecQ4 is essential for viability and fertility, and is required for most aspects of DNA replication during development.
ISSN:0012-1606
1095-564X
DOI:10.1016/j.ydbio.2008.08.006