Bianco, Julien N., Bergoglio, Valerie, Lin, Yea-Lih, Pillaire, Marie-Jeanne ORCID: 0000-0001-6866-7416, Schmitz, Anne-Lyne, Gilhodes, Julia, Lusque, Amelie, Mazieres, Julien, Lacroix-Triki, Magali, Roumeliotis, Theodoros, I, Choudhary, Jyoti, Moreaux, Jerome ORCID: 0000-0002-5717-3207, Hoffmann, Jean-Sebastien ORCID: 0000-0003-2222-354X, Tourriere, Helene and Pasero, Philippe ORCID: 0000-0001-5891-0822 (2019). Overexpression of Claspin and Timeless protects cancer cells from replication stress in a checkpoint-independent manner. Nat. Commun., 10. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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Abstract

Oncogene-induced replication stress (RS) promotes cancer development but also impedes tumor growth by activating anti-cancer barriers. To determine how cancer cells adapt to RS, we have monitored the expression of different components of the ATR-CHK1 pathway in primary tumor samples. We show that unlike upstream components of the pathway, the checkpoint mediators Claspin and Timeless are overexpressed in a coordinated manner. Remarkably, reducing the levels of Claspin and Timeless in HCT116 cells to pretumoral levels impeded fork progression without affecting checkpoint signaling. These data indicate that high level of Claspin and Timeless increase RS tolerance by protecting replication forks in cancer cells. Moreover, we report that primary fibroblasts adapt to oncogene-induced RS by spontaneously overexpressing Claspin and Timeless, independently of ATR signaling. Altogether, these data indicate that enhanced levels of Claspin and Timeless represent a gain of function that protects cancer cells from of oncogene-induced RS in a checkpoint-independent manner.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Bianco, Julien N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bergoglio, ValerieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lin, Yea-LihUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pillaire, Marie-JeanneUNSPECIFIEDorcid.org/0000-0001-6866-7416UNSPECIFIED
Schmitz, Anne-LyneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gilhodes, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lusque, AmelieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mazieres, JulienUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lacroix-Triki, MagaliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roumeliotis, Theodoros, IUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Choudhary, JyotiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moreaux, JeromeUNSPECIFIEDorcid.org/0000-0002-5717-3207UNSPECIFIED
Hoffmann, Jean-SebastienUNSPECIFIEDorcid.org/0000-0003-2222-354XUNSPECIFIED
Tourriere, HeleneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pasero, PhilippeUNSPECIFIEDorcid.org/0000-0001-5891-0822UNSPECIFIED
URN: urn:nbn:de:hbz:38-156362
DOI: 10.1038/s41467-019-08886-8
Journal or Publication Title: Nat. Commun.
Volume: 10
Date: 2019
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DNA-DAMAGE RESPONSE; ONCOGENE-INDUCED SENESCENCE; GENOMIC INSTABILITY; FORK PROTECTION; EUKARYOTIC DNA; BREAST-CANCER; UP-REGULATION; LUNG-CANCER; S PHASE; CHK1Multiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/15636

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