The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Loss of pRB causes centromere dysfunction and chromosomal instability
Open accessAbstract
Chromosome instability (CIN) is a common feature of tumor cells. By monitoring chromosome segregation, we show that depletion of the retinoblastoma protein (pRB) causes rates of missegregation comparable with those seen in CIN tumor cells. The retinoblastoma tumor suppressor is frequently inactivated in human cancers and is best known for its regulation of the G1/S-phase transition. Recent studies have shown that pRB inactivation also slows mitotic progression and promotes aneuploidy, but reasons for these phenotypes are not well understood. Here we describe the underlying mitotic defects of pRB-deficient cells that cause chromosome missegregation. Analysis of mitotic cells reveals that pRB depletion compromises centromeric localization of CAP-D3/condensin II and chromosome cohesion, leading to an increase in intercentromeric distance and deformation of centromeric structure. These defects promote merotelic attachment, resulting in failure of chromosome congression and an increased propensity for lagging chromosomes following mitotic delay. While complete loss of centromere function or chromosome cohesion would have catastrophic consequences, these more moderate defects allow pRB-deficient cells to proliferate but undermine the fidelity of mitosis, leading to whole-chromosome gains and losses. These observations explain an important consequence of RB1 inactivation, and suggest that subtle defects in centromere function are a frequent source of merotely and CIN in cancer.
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Cites
Nowell, P. C. (1976) · Science · doi:10.1126/science.959840 · Cited by 6,471
The retinoblastoma protein and cell cycle control
Weinberg, R. A. (1995) · Cell · doi:10.1016/0092-8674(95)90385-2 · Cited by 4,862
The landscape of somatic copy-number alteration across human cancers
Beroukhim, R., Mermel, C. H., Porter, D., Wei, G., Raychaudhuri, S., Donovan, J., Barretina, J., Boehm, J. S., Dobson, J., Urashima, M., et al. (2010) · Nature · doi:10.1038/nature08822 · Cited by 4,017
Cellular mechanisms of tumour suppression by the retinoblastoma gene
Burkhart, D. L., & Sage, J. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2399 · Cited by 974
Chromosome aberrations in solid tumors
Albertson, D. G., Collins, C., McCormick, F., & Gray, J. W. (2003) · Nature Genetics · doi:10.1038/ng1215 · Cited by 812
Hernando, E., Nahlé, Z., Juan, G., Diaz-Rodriguez, E., Alaminos, M., Hemann, M., Michel, L., Mittal, V., Gerald, W., Benezra, R., et al. (2004) · Nature · doi:10.1038/nature02820 · Cited by 562
Dimaras, H., Khetan, V., Halliday, W., Orlic, M., Prigoda, N. L., Piovesan, B., Marrano, P., Corson, T. W., Eagle, R. C., Squire, J. A., et al. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn024 · Cited by 351
The Retinoblastoma Protein Regulates Pericentric Heterochromatin
Isaac, C. E., Francis, S. M., Martens, A. L., Julian, L. M., Seifried, L. A., Erdmann, N., Binné, U. K., Harrington, L., Sicinski, P., Bérubé, N. G., et al. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.9.3659-3671.2006 · Cited by 128
Self-citationRb inactivation leads to E2F1-mediated DNA double-strand break accumulation
Pickering, M. T., & Kowalik, T. F. (2006) · Oncogene · doi:10.1038/sj.onc.1209103 · Cited by 108
RB acute loss induces centrosome amplification and aneuploidy in murine primary fibroblasts
Iovino, F., Lentini, L., Amato, A., & Di Leonardo, A. (2006) · Molecular Cancer · doi:10.1186/1476-4598-5-38 · Cited by 94
Cited by
RB1: a prototype tumor suppressor and an enigma
Dyson, N. J. (2016) · Genes & Development · doi:10.1101/gad.282145.116 · Cited by 435
Self-citationThe causes and consequences of polyploidy in normal development and cancer
Davoli, T., & de Lange, T. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154234 · Cited by 424
Rushlow, D. E., Mol, B. M., Kennett, J. Y., Yee, S., Pajovic, S., Thériault, B. L., Prigoda-Lee, N. L., Spencer, C., Dimaras, H., Corson, T. W., et al. (2013) · The Lancet Oncology · doi:10.1016/s1470-2045(13)70045-7 · Cited by 420
Schvartzman, J.-M., Duijf, P. H. G., Sotillo, R., Coker, C., & Benezra, R. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.04.017 · Cited by 181
Understanding pRb: toward the necessary development of targeted treatments for retinoblastoma
Sachdeva, U. M., & O’Brien, J. M. (2012) · Journal of Clinical Investigation · doi:10.1172/jci57114 · Cited by 67
Metadata
- Authors
- Manning, A. L., Longworth, M. S., & Dyson, N. J.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2010-06-15
- Volume
- 24
- Issue
- 13
- Pages
- 1364-1376
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2105081612
- Cited by
- 240
- References
- 11
- Type
- posted content
- Language
- en
- Open access
- diamond
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