ING2 controls the progression of DNA replication forks to maintain genome stability.
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.
Larrieu
Delphine
D
Molecular Bases of Lung Cancer Progression, INSERM U823, Institut Albert Bonniot, Université Joseph Fourier, Grenoble, France.
Ythier
Damien
D
Binet
Romuald
R
Brambilla
Christian
C
Brambilla
Elisabeth
E
Sengupta
Sagar
S
Pedeux
Rémy
R
D045744:Cell Line, Tumor; D004247:DNA / Q000096:biosynthesis / Q000235:genetics*; D004261:DNA Replication; D015894:Genome, Human; D042822:Genomic Instability; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D018398:Homeodomain Proteins; C444654:ING2 protein, human; D018809:Proliferating Cell Nuclear Antigen; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; D025521:Tumor Suppressor Proteins; D004247:DNA