NDLI: DNA Repair and Replication Fork Helicases Are Differentially Affected by Alkyl Phosphotriester Lesion

Content Provider	Journal of Biological Chemistry (JBC)
Author	Suhasini, Avvaru N. Sommers, Joshua A. Yu, Stephen Wu, Yuliang Xu, Ting Kelman, Zvi Kaplan, Daniel L. Jr, Robert M. Brosh Brosh, Robert M.
Abstract	DNA helicases are directly responsible for catalytically unwinding duplex DNA in an ATP-dependent and directionally specific manner and play essential roles in cellular nucleic acid metabolism. It has been conventionally thought that DNA helicases are inhibited by bulky covalent DNA adducts in a strand-specific manner. However, the effects of highly stable alkyl phosphotriester (PTE) lesions that are induced by chemical mutagens and refractory to DNA repair have not been previously studied for their effects on helicases. In this study, DNA repair and replication helicases were examined for unwinding a forked duplex DNA substrate harboring a single isopropyl PTE specifically positioned in the helicase-translocating or -nontranslocating strand within the double-stranded region. A comparison of SF2 helicases (RecQ, RECQ1, WRN, BLM, FANCJ, and ChlR1) with a SF1 DNA repair helicase (UvrD) and two replicative helicases (MCM and DnaB) demonstrates unique differences in the effect of the PTE on the DNA unwinding reactions catalyzed by these enzymes. All of the SF2 helicases tested were inhibited by the PTE lesion, whereas UvrD and the replication fork helicases were fully tolerant of the isopropyl backbone modification, irrespective of strand. Sequestration studies demonstrated that RECQ1 helicase was trapped by the PTE lesion only when it resided in the helicase-translocating strand. Our results are discussed in light of the current models for DNA unwinding by helicases that are likely to encounter sugar phosphate backbone damage during biological DNA transactions.
Related Links	http://www.jbc.org/content/287/23/19188.abstract
Ending Page	19198
Starting Page	19188
Page Count	11
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	23
Volume Number	287
DOI	10.1074/jbc.M112.352757
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2012-06-01
Access Restriction	Open
Subject Keyword	DNA Helicase DNA Repair DNA Replication Genetic Diseases Genomic Instability DNA Damage Carcinogenesis Mutagenesis Phosphotriester Sugar Phosphate Backbone Molecular Bases of Disease
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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