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Replicative stress induces intragenic transcription of the ASE1 gene that negatively regulates Ase1 activity.

Title: Replicative stress induces intragenic transcription of the ASE1 gene that negatively regulates Ase1 activity.
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Name(s): McKnight, Kelly, author
Liu, Hong, author
Wang, Yanchang, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2014-05-19
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Intragenic transcripts initiate within the coding region of a gene, thereby producing shorter mRNAs and proteins. Although intragenic transcripts are widely expressed [1], their role in the functional regulation of genes remains largely unknown. In budding yeast, DNA replication stress activates the S phase checkpoint that stabilizes replication forks and arrests cells in S phase with a short spindle [2-4]. When yeast cells were treated with hydroxyurea (HU) to block DNA synthesis and induce replication stress, we found that Ase1, a conserved spindle midzone protein [5], appeared as two short protein isoforms in addition to the full-length protein. We further demonstrated that the short isoforms result from intragenic transcription of ASE1, which depends on the S phase checkpoint. Blocking generation of the short isoforms leads to a destabilized S phase spindle, characterized by increased spindle dynamics and frequent spindle collapse. Because the short Ase1 isoforms localize at the spindle in HU-treated cells and overexpression of the short Ase1 isoforms impairs the spindle midzone localization of full-length Ase1, it is likely that the presence of short Ase1 isoforms stabilizes the spindle by antagonizing full-length Ase1. Together, our results reveal intragenic transcription as a unique mechanism to downregulate gene functions in response to DNA replication stress.
Identifier: FSU_pmch_24768052 (IID), 10.1016/j.cub.2014.03.040 (DOI), PMC4031280 (PMCID), 24768052 (RID), 24768052 (EID), S0960-9822(14)00332-7 (PII)
Grant Number: R01 GM102115, R15 GM097326, R01GM102115, R15GM097326
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4031280.
Subject(s): DNA Replication/drug effects
Enzyme Inhibitors/pharmacology
Gene Expression Regulation, Fungal/drug effects
Hydroxyurea/pharmacology
Microtubule-Associated Proteins/genetics
Microtubule-Associated Proteins/metabolism
Polymerase Chain Reaction
Protein Isoforms/genetics
Protein Isoforms/metabolism
Saccharomyces cerevisiae/genetics
Saccharomyces cerevisiae/metabolism
Saccharomyces cerevisiae Proteins/genetics
Saccharomyces cerevisiae Proteins/metabolism
Transcription, Genetic
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_24768052
Owner Institution: FSU
Is Part Of: Current biology : CB.
1879-0445
Issue: iss. 10, vol. 24

Choose the citation style.
McKnight, K., Liu, H., & Wang, Y. (2014). Replicative stress induces intragenic transcription of the ASE1 gene that negatively regulates Ase1 activity. Current Biology : Cb. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_24768052