FACT Is a Sensor of DNA Torsional Stress in Eukaryotic Cells

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FACT Is a Sensor of DNA Torsional Stress in Eukaryotic Cells

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Title: FACT Is a Sensor of DNA Torsional Stress in Eukaryotic Cells
Author(s):
Safina, A.;
Cheney, P.;
Pal, M.;
Brodsky, L.;
Ivanov, A.;
Kirsanov, K.;
Lesovaya, E.;
Naberezhnov, D.;
Nesher, E.;
Koman, I.;
Wang, D.;
Wang, J.;
Yakubovskaya, M.;
Winkler, Duane D.;
Gurova, K.
Date Created: 2017-01-13
Item Type: article
Keywords: Show Keywords
Description: Includes supplementary material
Abstract: Transitions of B-DNA to alternative DNA structures (ADS) can be triggered by negative torsional strain, which occurs during replication and transcription, and may lead to genomic instability. However, how ADS are recognized in cells is unclear. We found that the binding of candidate anticancer drug, curaxin, to cellular DNA results in uncoiling of nucleosomal DNA, accumulation of negative supercoiling and conversion of multiple regions of genomic DNA into left-handed Z-form. Histone chaperone FACT binds rapidly to the same regions via the SSRP1 subunit in curaxin-treated cells. In vitro binding of purified SSRP1 or its isolated CID domain to a methylated DNA fragment containing alternating purine/pyrimidines, which is prone to Z-DNA transition, is much stronger than to other types of DNA. We propose that FACT can recognize and bind Z-DNA or DNA in transition from a B to Z form. Binding of FACT to these genomic regions triggers a p53 response. Furthermore, FACT has been shown to bind to other types of ADS through a different structural domain, which also leads to p53 activation. Thus, we propose that FACT acts as a sensor of ADS formation in cells. Recognition of ADS by FACT followed by a p53 response may explain the role of FACT in DNA damage prevention. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.
ISSN: 1362-4962
Source: Nucleic Acids Research
Link to Related Resource: http://dx.doi.org/10.1093/nar/gkw1366
Persistent Link: http://hdl.handle.net/10735.1/6135
Bibliographic Citation: Safina, A., P. Cheney, M. Pal, L. Brodsky, et al. 2017. "FACT is a sensor of DNA torsional stress in eukaryotic cells." Nucleic Acids Research 45(4), doi:10.1093/nar/gkw1366
Terms of Use: CC BY-NC 4.0/ (Attribution-NonCommercial)
©2017 The Authors

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CC BY-NC 4.0/ (Attribution-NonCommercial) Except where otherwise noted, this item's license is described as CC BY-NC 4.0/ (Attribution-NonCommercial)