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Mutual correction of faulty PCNA subunits in temperature-sensitive lethal mus209 mutants of Drosophila melanogaster

Henderson, Daryl S. and Wiegand, Ulrich K. and Norman, David G. and Glover, David M. (2000) Mutual correction of faulty PCNA subunits in temperature-sensitive lethal mus209 mutants of Drosophila melanogaster. Genetics, 154 (4). pp. 1721-1733. ISSN 0016-6731. PMCID PMC1461035. https://resolver.caltech.edu/CaltechAUTHORS:20201005-153558029

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Abstract

Proliferating cell nuclear antigen (PCNA) functions in DNA replication as a processivity factor for polymerases delta and epsilon, and in multiple DNA repair processes. We describe two temperature-sensitive lethal alleles (mus209^(B1) and mus209^(2735)) of the Drosophila PCNA gene that, at temperatures permissive for growth, result in hypersensitivity to DNA-damaging agents, suppression of position-effect variegation, and female sterility in which ovaries are underdeveloped and do not produce eggs. We show by mosaic analysis that the sterility of mus209(B1) is partly due to a failure of germ-line cells to proliferate. Strikingly, mus209^(B1) and mus209^(2735) interact to restore partial fertility to heteroallelic females, revealing additional roles for PCNA in ovarian development, meiotic recombination, and embryogenesis. We further show that, although mus209^(B1) and mus209^(2735) homozygotes are each defective in repair of transposase-induced DNA double-strand breaks in somatic cells, this defect is substantially reversed in the heteroallelic mutant genotype. These novel mutations map to adjacent sites on the three-dimensional structure of PCNA, which was unexpected in the context of this observed interallelic complementation. These mutations, as well as four others we describe, reveal new relationships between the structure and function of PCNA.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://www.genetics.org/content/154/4/1721.longPublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1461035/PubMed CentralArticle
ORCID:
AuthorORCID
Glover, David M.0000-0003-0956-0103
Additional Information:© 2000 by the Genetics Society of America. Received September 3, 1999. Accepted December 28, 1999. We are grateful to Ken Burtis, Cayetano Gonzalez, Scott Hawley, John Kiger, Hiroyuki Ohkura, Terry Orr-Weaver, Alastair Philp, Helen White-Cooper, and Rochele Yamamoto for their helpful discussions and critical comments on various aspects of this work. We thank Fiona Cullen and Sabine Corbach for technical assistance, Trudi Schüpbach for providing Fs(2)D and advice, and Cathy Salles for the ovo-lacZ reporter line. This work was supported by the Cancer Research Campaign.
Funders:
Funding AgencyGrant Number
Cancer Research CampaignUNSPECIFIED
Issue or Number:4
PubMed Central ID:PMC1461035
Record Number:CaltechAUTHORS:20201005-153558029
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20201005-153558029
Official Citation:Mutual Correction of Faulty PCNA Subunits in Temperature-Sensitive Lethal mus209 Mutants of Drosophila melanogaster Daryl S. Henderson, Ulrich K. Wiegand, David G. Norman and David M. Glover GENETICS April 1, 2000 vol. 154 no. 4 1721-1733
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:105821
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:06 Oct 2020 14:16
Last Modified:06 Oct 2020 14:16

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