Mutation of the Drosophila homologue of the Myb protooncogene causes genomic instability

J Robert Manak; Nesanet Mitiku; Joseph S Lipsick

doi:10.1073/pnas.122231599

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Mutation of the Drosophila homologue of the Myb protooncogene causes genomic instability

Journal article

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Mutation of the Drosophila homologue of the Myb protooncogene causes genomic instability

J Robert Manak, Nesanet Mitiku and Joseph S Lipsick

Proceedings of the National Academy of Sciences - PNAS, Vol.99(11), pp.7438-7443

05/28/2002

DOI: 10.1073/pnas.122231599

PMCID: PMC124249

PMID: 12032301

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Abstract

Vertebrates have three related Myb genes. The c-Myb protooncogene is required for definitive hematopoiesis in mice and when mutated causes leukemias and lymphomas in birds and mammals. The A-Myb gene is required for spermatogenesis and mammary gland proliferation in mice. The ubiquitously expressed B-Myb gene is essential for early embryonic development in mice and is directly regulated by the p16/cyclin D/Rb family/E2F pathway along with many critical S-phase genes. Drosophila has a single Myb gene most closely related to B-Myb. We have isolated two late-larval lethal alleles of Drosophila Myb. Mutant imaginal discs show an increased number of cells arrested in M phase. Mutant mitotic cells display a variety of abnormalities including spindle defects and increased polyploidy and aneuploidy. Remarkably, some mutant cells have an aberrant S- to M-phase transition in which replicating chromosomes undergo premature histone phosphorylation and chromosomal condensation. These results suggest that the absence of Drosophila Myb causes a defect in S phase that may result in M-phase abnormalities. Consistent with a role for Drosophila Myb during S phase, we detected Dm-Myb protein in S-phase nuclei of wild-type mitotic cells as well as endocycling cells, which lack both an M phase and cyclin B expression. Moreover, we found that the Dm-Myb protein is concentrated in regions of S-phase nuclei that are actively undergoing DNA replication. Together these findings imply that Dm-Myb provides an essential nontranscriptional function during chromosomal replication.

Polyploidy

Animals

Gene Expression Regulation, Developmental

Genes, myb - genetics

Karyotyping

DNA Replication - genetics

Proto-Oncogene Proteins c-myb - genetics

Aneuploidy

Drosophila - embryology

Mutation

Drosophila - genetics

Details

Title: Subtitle: Mutation of the Drosophila homologue of the Myb protooncogene causes genomic instability
Creators: J Robert Manak - Department of Pathology, Stanford University School of Medicine, Room L216, 300 Pasteur Drive, Stanford, CA 94305-5324, USA
Nesanet Mitiku
Joseph S Lipsick
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.99(11), pp.7438-7443
DOI: 10.1073/pnas.122231599
PMID: 12032301
PMCID: PMC124249
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: United States
Language: English
Date published: 05/28/2002
Academic Unit: Stead Family Department of Pediatrics; Biology; Craniofacial Anomalies Research Center
Record Identifier: 9983992098302771

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