The Drosophila mus101 gene, which links DNA repair, replication and condensation of heterochromatin in mitosis, encodes a protein with seven BRCA1 C-terminus domains
| Autor: | Yutaka Yamamoto, David M. Glover, Robert D. C. Saunders, J.Myles Axton, Daryl S. Henderson, Rochele R. Yamamoto |
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| Jazyk: | angličtina |
| Rok vydání: | 2000 |
| Předmět: |
DNA Replication
Male X Chromosome Positional cloning DNA Repair DNA repair Heterochromatin Molecular Sequence Data Genes BRCA1 Cell Cycle Proteins Genes Insect Biology Gene duplication Genetics Animals Drosophila Proteins Amino Acid Sequence Gene Mitosis Sequence Homology Amino Acid BRCA1 Protein DNA replication Chromosome Mapping Drosophila melanogaster Phenotype Mutagenesis Larva Insect Proteins Female Genes Lethal Infertility Female Sequence Alignment Drosophila Protein Research Article |
| Popis: | The mutagen-sensitive-101 (mus101) gene of Drosophila melanogaster was first identified 25 years ago through mutations conferring larval hypersensitivity to DNA-damaging agents. Other alleles of mus101 causing different phenotypes were later isolated: a female sterile allele results in a defect in a tissue-specific form of DNA synthesis (chorion gene amplification) and lethal alleles cause mitotic chromosome instability that can be observed genetically and cytologically. The latter phenotype presents as a striking failure of mitotic chromosomes of larval neuroblasts to undergo condensation of pericentric heterochromatic regions, as we show for a newly described mutant carrying lethal allele mus101lcd. To gain further insight into the function of the Mus101 protein we have molecularly cloned the gene using a positional cloning strategy. We report here that mus101 encodes a member of the BRCT (BRCA1 C terminus) domain superfamily of proteins implicated in DNA repair and cell cycle checkpoint control. Mus101, which contains seven BRCT domains distributed throughout its length, is most similar to human TopBP1, a protein identified through its in vitro association with DNA topoisomerase IIβ. Mus101 also shares sequence similarity with the fission yeast Rad4/Cut5 protein required for repair, replication, and checkpoint control, suggesting that the two proteins may be functional homologs. |
| Databáze: | OpenAIRE |
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