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The Drosophila mus101 gene, which links DNA repair, replication and condensation of heterochromatin in mitosis, encodes a protein with seven BRCA1 C-terminus domains

Yamamoto, Rochelle R. and Axton, J. Myles and Yamamoto, Yutaka and Saunders, Robert D. C. and Glover, David M. and Henderson, Daryl S. (2000) The Drosophila mus101 gene, which links DNA repair, replication and condensation of heterochromatin in mitosis, encodes a protein with seven BRCA1 C-terminus domains. Genetics, 156 (2). pp. 711-721. ISSN 0016-6731. PMCID PMC1461266.

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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 mus101^(lcd). 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 IIbeta. 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.

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Glover, David M.0000-0003-0956-0103
Additional Information:© 2000 by the Genetics Society of America. Received February 22, 2000. Accepted June 8, 2000. Published online October 1, 2000. We thank A. Schalet, A. Carpenter, M. Gatti, B. Baker, V. Lloyd, D. Sinclair, E. Frei, and S. Krishnan for providing fly stocks or cloned DNA and helpful information. We are grateful to F. Cullen, L. Campbell, C. Salles, D. Callister, and A. Bain for expert technical assistance, and past and present members of the lab for support and helpful discussion, especially P. Deak, E. Wojcik, H. Ohkura, R. Wiegand, and S. Brand. R.R.Y. was funded by the Brazilian agency CNPq. This work was made possible by grants from the Cancer Research Campaign.
Funding AgencyGrant Number
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)UNSPECIFIED
Cancer Research CampaignUNSPECIFIED
Issue or Number:2
PubMed Central ID:PMC1461266
Record Number:CaltechAUTHORS:20200930-144315567
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Official Citation:The Drosophila mus101 Gene, Which Links DNA Repair, Replication and Condensation of Heterochromatin in Mitosis, Encodes a Protein With Seven BRCA1 C-Terminus Domains Rochele R. Yamamoto, J. Myles Axton, Yutaka Yamamoto, Robert D. C. Saunders, David M. Glover and Daryl S. Henderson GENETICS October 1, 2000 vol. 156 no. 2 711-721
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:105696
Deposited By: George Porter
Deposited On:01 Oct 2020 14:21
Last Modified:01 Oct 2020 14:21

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