Haploinsufficiency of an RB-E2F1-Condensin II complex causes replication stress and contributes to mesenchymal cancers [γH2AX localization]

ABSTRACT: Genome instability is a characteristic of malignant cells, however, evidence for its contribution to tumorigenesis has been enigmatic. In this study we demonstrate that a complex containing the retinoblastoma protein, E2F1, and Condensin II localizes to major satellite repeats at pericentromeres. In the absence of this complex, this genomic region fails to properly replicate and H2AX phosphorylation at pericentromeric repeats is increased. Our data indicates that these lesions contribute to defective chromosome segregation in the ensuing mitosis. Surprisingly, loss of even one copy of the retinoblastoma gene was sufficient to reduce recruitment of Condensin II to pericentromeres and cause this phenotype. Furthermore, we determined that human RB1 mutation status in cancers of mesenchymal or

ORGANISM(S): Mus musculus

SUBMITTER: Fred Dick 

PROVIDER: E-GEOD-51558 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress