Journal
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 34
Volume 34, Issue -, Pages 265-288Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-cellbio-100617-062653
Keywords
constitutive heterochromatin; pericentromeres; genome stability; chromosome segregation; repetitive DNA; DNA repair
Categories
Funding
- NIGMS NIH HHS [R01 GM117420] Funding Source: Medline
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM117420] Funding Source: NIH RePORTER
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Constitutive heterochromatin is a major component of the eukaryotic nucleus and is essential for the maintenance of genome stability. Highly concentrated at pericentromeric and telomeric domains, heterochromatin is riddled with repetitive sequences and has evolved specific ways to compartmentalize, silence, and repair repeats. The delicate balance between heterochromatin epigenetic maintenance and cellular processes such as mitosis and DNA repair and replication reveals a highly dynamic and plastic chromatin domain that can be perturbed by multiple mechanisms, with far-reaching consequences for genome integrity. Indeed, heterochromatin dysfunction provokes genetic turmoil by inducing aberrant repeat repair, chromosome segregation errors, transposon activation, and replication stress and is strongly implicated in aging and tumorigenesis. Here, we summarize the general principles of heterochromatin structure and function, discuss the importance of its maintenance for genome integrity, and propose that more comprehensive analyses of heterochromatin roles in tumorigenesis will be integral to future innovations in cancer treatment.
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