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ING2 controls the progression of DNA replication forks to maintain genome stability
Author(s) -
Larrieu Delphine,
Ythier Damien,
Binet Romuald,
Brambilla Christian,
Brambilla Elisabeth,
Sengupta Sagar,
Pedeux Rémy
Publication year - 2009
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2009.180
Subject(s) - biology , genome instability , dna replication , chromatin , dna , microbiology and biotechnology , genetics , dna damage
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.