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Crosstalk between chromatin state and DNA damage response in cellular senescence and cancer

Nature Reviews Cancer volume 12, pages 709–720 (2012)Cite this article

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Abstract

The generation of DNA lesions and the resulting activation of DNA damage response (DDR) pathways are both affected by the chromatin status at the site of damaged DNA. In turn, DDR activation affects the chromatin at both the damaged site and across the whole genome. Cellular senescence and cancer are associated with the engagement of the DDR pathways and with profound chromatin changes. In this Opinion article, we discuss the interplay between chromatin and DDR factors in the context of cellular senescence that is induced by oncogenes and in cancer.

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Figure 1: The DNA damage response
Figure 2: Chromatin remodellers and histone modifiers following DNA damage induction.
Figure 3: Histone modifications involved in DDR signalling.
Figure 4: Proposed model of the connection between chromatin alterations, the DDR and OIS.

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Acknowledgements

F.d'A.d.F. laboratory is supported by FIRC (Fondazione Italiana per la Ricerca sul Cancro), AIRC (Associazione Italiana per la Ricerca sul Cancro), HFSP (Human Frontier Science Program), Cariplo Foundation, FP7-PEOPLE-2012-ITN (CodAge).

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Author notes

  1. Fabrizio d'Adda di Fagagna

    Present address: Fabrizio d'Adda di Fagagna is at Istituto di Genetica Molecolare – Consiglio Nazionale delle Ricerche, Via Abbiategrasso 207, 27100 Pavia, Italy.,

  2. Gabriele Sulli

    Present address: Gabriele Sulli's present address is at The Salk Institute for Biological Studies, California 92037, USA.,

  3. Raffaella Di Micco

    Present address: Raffaella Di Micco's present address is at The New York University School of Medicine, Department of Pathology, New York 10016, USA.,

Authors and Affiliations

  1. Gabriele Sulli, Raffaella Di Micco and Fabrizio d'Adda di Fagagna are at IFOM Foundation - FIRC Institute of Molecular Oncology Foundation, Milan 20139, Italy.,

    Gabriele Sulli, Raffaella Di Micco & Fabrizio d'Adda di Fagagna

  2. Fabrizio d'Adda di Fagagna is at Istituto di Genetica Molecolare – Consiglio Nazionale delle Ricerche, Via Abbiategrasso 207, 27100 Pavia, Italy.,

    Raffaella Di Micco

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  1. Gabriele Sulli
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Correspondence to Fabrizio d'Adda di Fagagna.

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Sulli, G., Di Micco, R. & di Fagagna, F. Crosstalk between chromatin state and DNA damage response in cellular senescence and cancer. Nat Rev Cancer 12, 709–720 (2012). https://doi.org/10.1038/nrc3344

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