ING2 controls the progression of DNA replication forks to maintain genome stability |
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Authors: | Delphine Larrieu Damien Ythier Romuald Binet Christian Brambilla Elisabeth Brambilla Sagar Sengupta Rémy Pedeux |
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Institution: | 1. Molecular Bases of Lung Cancer Progression, INSERM U823, Institut Albert Bonniot, Université Joseph Fourier, Grenoble, 38706 Cedex, France;2. National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067 India;3. INSERM U917, IFR140, Faculté de Médecine, Université de Rennes 1, 35043 Rennes, Cedex, France |
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Abstract: | Inhibitor of growth 2 (ING2) is a candidate tumour suppressor gene the expression of which is frequently lost in tumours. Here, we identified a new function for ING2 in the control of DNA replication and in the maintenance of genome stability. Global replication rate was markedly reduced during normal S‐phase in small interfering RNA (siRNA) ING2 cells, as seen in a DNA fibre spreading experiment. Accordingly, we found that ING2 interacts with proliferating cell nuclear antigen and regulates its amount to the chromatin fraction, allowing normal replication progression and normal cell proliferation. Deregulation of DNA replication has been previously associated with genome instability. Hence, a high proportion of siRNA ING2 cells presented endoreduplication of their genome as well as an increased frequency of sister chromatid exchange. Thus, we propose for the first time that ING2 might function as a tumour suppressor gene by directly maintaining DNA integrity. |
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Keywords: | DNA replication genome stability ING2 PCNA tumour suppressor |
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