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Abstract
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.