TY - JOUR
T1 - Aneuploidy in Cancer and Aging
AU - Naylor, Ryan M.
AU - Van Deursen, Jan M.
N1 - Publisher Copyright:
© 2016 by Annual Reviews. All rights reserved.
PY - 2016/11/23
Y1 - 2016/11/23
N2 - Chromosomal instability (CIN), the persistent inability of a cell to faithfully segregate its genome, is a feature of many cancer cells. It stands to reason that CIN enables the acquisition of multiple cancer hallmarks; however, there is a growing body of evidence suggesting that CIN impairs cellular fitness and prevents neoplastic transformation. Here, we suggest a new perspective to reconcile this apparent paradox and share an unexpected link between aneuploidy and aging that was discovered through attempts to investigate the CIN-cancer relationship. Additionally, we provide a comprehensive overview of the function and regulation of the anaphase-promoting complex, an E3 ubiquitin ligase that mediates high-fidelity chromosome segregation, and describe the mechanisms that lead to whole-chromosome gain or loss. With this review, we aim to expand our understanding of the role of CIN in cancer and aging with the long-term objective of harnessing this information for the advancement of patient care.
AB - Chromosomal instability (CIN), the persistent inability of a cell to faithfully segregate its genome, is a feature of many cancer cells. It stands to reason that CIN enables the acquisition of multiple cancer hallmarks; however, there is a growing body of evidence suggesting that CIN impairs cellular fitness and prevents neoplastic transformation. Here, we suggest a new perspective to reconcile this apparent paradox and share an unexpected link between aneuploidy and aging that was discovered through attempts to investigate the CIN-cancer relationship. Additionally, we provide a comprehensive overview of the function and regulation of the anaphase-promoting complex, an E3 ubiquitin ligase that mediates high-fidelity chromosome segregation, and describe the mechanisms that lead to whole-chromosome gain or loss. With this review, we aim to expand our understanding of the role of CIN in cancer and aging with the long-term objective of harnessing this information for the advancement of patient care.
KW - Anaphase-promoting complex/cyclosome
KW - Chromosomal instability
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U2 - 10.1146/annurev-genet-120215-035303
DO - 10.1146/annurev-genet-120215-035303
M3 - Review article
C2 - 27893964
AN - SCOPUS:85000643937
SN - 0066-4197
VL - 50
SP - 45
EP - 66
JO - Annual Review of Genetics
JF - Annual Review of Genetics
ER -