دورية أكاديمية

Compensation for the absence of the catalytically active half of DNA polymerase ε in yeast by positively selected mutations in CDC28.

التفاصيل البيبلوغرافية
العنوان: Compensation for the absence of the catalytically active half of DNA polymerase ε in yeast by positively selected mutations in CDC28.
المؤلفون: Stepchenkova EI; Laboratory of Mutagenesis and Genetic Toxicology, Vavilov Institute of General Genetics, Saint-Petersburg Branch, Russian Academy of Sciences, Saint-Petersburg 199034, Russia.; Department of Genetics and Biotechnology, Saint-Petersburg State University, Saint-Petersburg 199034, Russia.; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA., Zhuk AS; ITMO University, Saint-Petersburg 191002, Russia., Cui J; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA., Tarakhovskaya ER; Laboratory of Mutagenesis and Genetic Toxicology, Vavilov Institute of General Genetics, Saint-Petersburg Branch, Russian Academy of Sciences, Saint-Petersburg 199034, Russia.; Department of Plant Physiology and Biochemistry, Saint-Petersburg State University, Saint-Petersburg 199034, Russia., Barbari SR; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA., Shcherbakova PV; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA., Polev DE; Research Resource Center 'Biobank,' Research Park, Saint-Petersburg State University, Saint-Petersburg 198504, Russia., Fedorov R; Department of Mathematics, University of Pittsburgh, PA 15213, USA., Poliakov E; Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA., Rogozin IB; National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA., Lada AG; Department of Microbiology and Molecular Genetics, University of California Davis, Davis, CA 92697, USA., Pavlov YI; Department of Genetics and Biotechnology, Saint-Petersburg State University, Saint-Petersburg 199034, Russia.; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA.; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA.; Department of Microbiology and Pathology, University of Nebraska Medical Center, Omaha, NE 68198, USA.; Department of Genetics Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
المصدر: Genetics [Genetics] 2021 Jun 24; Vol. 218 (2).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: United States NLM ID: 0374636 Publication Model: Print Cited Medium: Internet ISSN: 1943-2631 (Electronic) Linking ISSN: 00166731 NLM ISO Abbreviation: Genetics Subsets: MEDLINE
أسماء مطبوعة: Publication: 2021- : [Oxford] : Oxford University Press
Original Publication: Austin, Tex. [etc.]
مواضيع طبية MeSH: DNA Replication*, CDC28 Protein Kinase, S cerevisiae/*genetics , CDC28 Protein Kinase, S cerevisiae/*metabolism , DNA Polymerase II/*genetics , Saccharomyces cerevisiae/*genetics, DNA Polymerase II/metabolism ; DNA, Fungal ; Genome, Fungal ; Mutagenesis ; Mutation Rate ; Polymorphism, Single Nucleotide ; Saccharomyces cerevisiae/enzymology ; Selection, Genetic
مستخلص: Current eukaryotic replication models postulate that leading and lagging DNA strands are replicated predominantly by dedicated DNA polymerases. The catalytic subunit of the leading strand DNA polymerase ε, Pol2, consists of two halves made of two different ancestral B-family DNA polymerases. Counterintuitively, the catalytically active N-terminal half is dispensable, while the inactive C-terminal part is required for viability. Despite extensive studies of yeast Saccharomyces cerevisiae strains lacking the active N-terminal half, it is still unclear how these strains survive and recover. We designed a robust method for constructing mutants with only the C-terminal part of Pol2. Strains without the active polymerase part show severe growth defects, sensitivity to replication inhibitors, chromosomal instability, and elevated spontaneous mutagenesis. Intriguingly, the slow-growing mutant strains rapidly accumulate fast-growing clones. Analysis of genomic DNA sequences of these clones revealed that the adaptation to the loss of the catalytic N-terminal part of Pol2 occurs by a positive selection of mutants with improved growth. Elevated mutation rates help generate sufficient numbers of these variants. Single nucleotide changes in the cell cycle-dependent kinase gene, CDC28, improve the growth of strains lacking the N-terminal part of Pol2, and rescue their sensitivity to replication inhibitors and, in parallel, lower mutation rates. Our study predicts that changes in mammalian homologs of cyclin-dependent kinases may contribute to cellular responses to the leading strand polymerase defects.
(© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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معلومات مُعتمدة: P20 GM103427 United States GM NIGMS NIH HHS; P30 GM110768 United States GM NIGMS NIH HHS; R01 CA239688 United States CA NCI NIH HHS; R01 ES015869 United States ES NIEHS NIH HHS; P30 CA036727 United States CA NCI NIH HHS; P30 GM106397 United States GM NIGMS NIH HHS; T32 CA009476 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: CDC28; DNA polymerase ε; DNA replication; cyclin-dependent kinase; illegitimate mating; leading strand; mutation rates; yeast
سلسلة جزيئية: figshare 10.25386/genetics.14357234
المشرفين على المادة: 0 (DNA, Fungal)
EC 2.7.11.22 (CDC28 Protein Kinase, S cerevisiae)
EC 2.7.7.7 (DNA Polymerase II)
تواريخ الأحداث: Date Created: 20210412 Date Completed: 20220221 Latest Revision: 20220413
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC8225352
DOI: 10.1093/genetics/iyab060
PMID: 33844024
قاعدة البيانات: MEDLINE
الوصف
تدمد:1943-2631
DOI:10.1093/genetics/iyab060