CSA and CSB play a role in the response to DNA breaks

Barbara Pascucci; Alessandra Fragale; Veronica Marabitti; Giuseppe Leuzzi; Angelo Salvatore Calcagnile; Eleonora Parlanti; Annapaola Franchitto; Eugenia Dogliotti; Mariarosaria D’Errico

doi:10.18632/oncotarget.24342

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Research Papers:

CSA and CSB play a role in the response to DNA breaks

Barbara Pascucci, Alessandra Fragale, Veronica Marabitti, Giuseppe Leuzzi, Angelo Salvatore Calcagnile, Eleonora Parlanti, Annapaola Franchitto, Eugenia Dogliotti _ and Mariarosaria D’Errico

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Oncotarget. 2018; 9:11581-11591. https://doi.org/10.18632/oncotarget.24342

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Abstract

Barbara Pascucci1,3, Alessandra Fragale2, Veronica Marabitti3, Giuseppe Leuzzi3,4, Angelo Salvatore Calcagnile3, Eleonora Parlanti3, Annapaola Franchitto3, Eugenia Dogliotti3 and Mariarosaria D’Errico3

1Institute of Cristallography, Consiglio Nazionale delle Ricerche, Roma, Italy

2Section of Tumor Immunology, Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Roma, Italy

3Section of Mechanisms, Biomarkers and Models, Department of Environment and Health, Istituto Superiore di Sanità, Roma, Italy

4Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA

Correspondence to:

Eugenia Dogliotti, email: [email protected]

Mariarosaria D’Errico, email: [email protected]

Keywords: Cockayne syndrome; DNA damage; DNA repair; γ-H2AX

Received: September 07, 2017 Accepted: January 19, 2018 Published: January 29, 2018

ABSTRACT

CS proteins have been involved in the repair of a wide variety of DNA lesions. Here, we analyse the role of CS proteins in DNA break repair by studying histone H2AX phosphorylation in different cell cycle phases and DNA break repair by comet assay in CS-A and CS-B primary and transformed cells. Following methyl methane sulphate treatment a significant accumulation of unrepaired single strand breaks was detected in CS cells as compared to normal cells, leading to accumulation of double strand breaks in S and G2 phases. A delay in DSBs repair and accumulation in S and G2 phases were also observed following IR exposure. These data confirm the role of CSB in the suppression of NHEJ in S and G2 phase cells and extend this function to CSA. However, the repair kinetics of double strand breaks showed unique features for CS-A and CS-B cells suggesting that these proteins may act at different times along DNA break repair.

The involvement of CS proteins in the repair of DNA breaks may play an important role in the clinical features of CS patients.

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Research Papers:

CSA and CSB play a role in the response to DNA breaks

Abstract