Histone chaperone FACT is essential to overcome replication stress in mammalian cells.

Oncogene
Laura PrendergastKaterina Gurova

Abstract

The histone chaperone FACT is upregulated during mammary tumorigenesis and necessary for the viability and growth of breast tumor cells. We established that only proliferating tumor cells are sensitive to FACT knockdown, suggesting that FACT functions during DNA replication in tumor cells but not in normal cells. We hypothesized that the basal level of replication stress defines the FACT dependence of cells. Using genetic and chemical tools, we demonstrated that FACT is needed to overcome replication stress. In the absence of FACT during replication stress, the MCM2-7 helicase dissociates from chromatin, resulting in the absence of ssDNA accumulation, RPA binding, and activation of the ATR/CHK1 checkpoint response. Without this response, stalled replication forks are not stabilized, and new origin firing cannot be prevented, leading to the accumulation of DNA damage and cell death. Thus, we propose a novel role for FACT as a factor preventing helicase dissociation from chromatin during replication stress.

References

Sep 17, 1996·Proceedings of the National Academy of Sciences of the United States of America·V S OssovskayaA V Gudkov
Dec 23, 1999·The Journal of Biological Chemistry·S T KimM B Kastan
Jan 27, 2000·Cell·D Hanahan, R A Weinberg
Oct 2, 2003·Proceedings of the National Academy of Sciences of the United States of America·Maarten Hoek, Bruce Stillman
Jun 16, 2004·The Journal of Cell Biology·Susanna Ekholm-ReedSteven I Reed
Jan 25, 2005·Molecular Cell·Anja GrothGeneviève Almouzni
Dec 1, 2006·Nature·Raffaella Di MiccoFabrizio d'Adda di Fagagna
Dec 2, 2009·The Plant Journal : for Cell and Molecular Biology·Ihab B LolasKlaus D Grasser
Feb 17, 2010·Journal of Biomedical Science·Bertrand Chin-Ming TanSheng-Chung Lee
May 4, 2010·PloS One·Thomas W SpiesserEdda Klipp
Dec 24, 2010·The EMBO Journal·Armelle CorpetGeneviève Almouzni
Aug 13, 2011·Science Translational Medicine·Alexander V GasparianKaterina V Gurova
Jun 13, 2012·Cancer Prevention Research·Igor E KomanKaterina V Gurova
Sep 18, 2012·Biochimica Et Biophysica Acta·Olga I KulaevaVasily M Studitsky
Jan 1, 2014·The Journal of Cell Biology·Jakob MejlvangAnja Groth
Jan 7, 2014·PloS One·Warren P VothDavid J Stillman
Nov 6, 2015·Science Translational Medicine·Daniel R CarterGlenn M Marshall
Mar 12, 2016·Genes & Development·Yasuo TsunakaKosuke Morikawa
Apr 8, 2016·Cell Reports·Constance Qiao Xin YeoChit Fang Cheok
Nov 10, 2016·Cell Reports·Ina KlusmannMatthias Dobbelstein
Jun 18, 2017·Molecular Cell·Luis ToledoJiri Lukas
Oct 22, 2017·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Zhaojun QiuJunran Zhang
Oct 16, 2018·Stem Cells and Development·Zuolian ShenDean Tantin

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Citations

Nov 10, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Lucia Falbo, Vincenzo Costanzo
Mar 24, 2021·Molecular and Cellular Biology·Ann K Hogan, Daniel R Foltz
Nov 18, 2021·The EMBO Journal·Ann K HoganDaniel R Foltz
Nov 26, 2021·Biochemical Society Transactions·Aleix Bayona-Feliu, Andrés Aguilera
Jan 22, 2022·Nucleic Acids Research·Barbara SafaricKarl E Duderstadt

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Methods Mentioned

BETA
transfection
flow cytometry
Protein Assay
caspase
Assay
FCS

Software Mentioned

WinList
FCS Express
AxioVision
WinList [UNK]
FACT
ImageJ

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