RB1 binds condensin II

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R-HSA-2172666
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Reaction
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Homo sapiens
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RB1 binds the condensin II complex through interaction with the NCAPD3 subunit of condensin II. This interaction is E2F independent and is important for targeting of the condensin II complex to chromatin (Longworth et al. 2008). RB1 may be particularly important for targeting of the condensin II complex to centromeres (Manning et al. 2010). RB1 deficient cells exhibit chromosome condensation defects and are prone to aneuploidy caused by aberrant chromosomal segregation. Therefore, tumor suppressor role of RB1 is based both on E2F-dependent control of G1/S transition, as well as on E2F-independent maintenance of genomic stability through regulation of mitotic chromosome condensation (Longworth et al. 20008, Coschi et al. 2010, Manning et al. 2010).

The role of RB1 in the maintenance of genomic stability is supported by studies of the childhood eye cancer retinoblastoma and its precursor, retinoma. Retinoma, a quiescent precursor of malignant retinoblastoma with functional loss of both RB1 alleles, is genomically unstable (Dimaras et al. 2008). Also, while the majority of retinoblastoma tumors are caused by the loss-of-function of the tumor suppressor gene RB1, ~2% of retinoblastoma tumors in unilaterally affected patients are initiated by a high level amplification of MYCN gene, in the presence of two functional, unmutated RB1 alleles. These tumors, with normal RB1 and amplified MYCN show a much lower level of genomic instability than retinoblastoma tumors with RB1 loss-of-function (Rushlow et al. 2013).

Literature References
PubMed ID Title Journal Year
18211953 Loss of RB1 induces non-proliferative retinoma: increasing genomic instability correlates with progression to retinoblastoma

Dimaras, H, Khetan, V, Halliday, W, Orlic, M, Prigoda, NL, Piovesan, B, Marrano, P, Corson, TW, Eagle, RC, Squire, JA, Gallie, BL

Hum. Mol. Genet. 2008
20551165 Loss of pRB causes centromere dysfunction and chromosomal instability

Manning, AL, Longworth, MS, Dyson, NJ

Genes Dev 2010
20551166 Mitotic chromosome condensation mediated by the retinoblastoma protein is tumor-suppressive

Coschi, CH, Martens, AL, Ritchie, K, Francis, SM, Chakrabarti, S, Berube, NG, Dick, FA

Genes Dev. 2010
23498719 Characterisation of retinoblastomas without RB1 mutations: genomic, gene expression, and clinical studies

Rushlow, DE, Mol, BM, Kennett, JY, Yee, S, Pajovic, S, Thériault, BL, Prigoda-Lee, NL, Spencer, C, Dimaras, H, Corson, TW, Pang, R, Massey, C, Godbout, R, Jiang, Z, Zacksenhaus, E, Paton, K, Moll, AC, Houdayer, C, Raizis, A, Halliday, W, Lam, WL, Boutros, PC, Lohmann, D, Dorsman, JC, Gallie, BL

Lancet Oncol. 2013
18367646 RBF1 promotes chromatin condensation through a conserved interaction with the Condensin II protein dCAP-D3

Longworth, MS, Herr, A, Ji, JY, Dyson, NJ

Genes Dev 2008
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