Cited by 500Genomics and Chromatin DynamicsChromosomal and Genetic VariationsNuclear Structure and Function

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Heterochromatin: Guardian of the Genome

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Janssen, Aniek, Colmenares, Serafin U., Karpen, Gary H.·2018·Annual Review of Cell and Developmental Biology

DOI 10.1146/annurev-cellbio-100617-062653

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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.

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Authors: Janssen, A., Colmenares, S. U., & Karpen, G. H.
Affiliations: Lawrence Berkeley National Laboratory (US)
Corresponding author: Karpen, Gary H.
ORCID: Janssen, Aniek
Colmenares, Serafin U.
Karpen, Gary H.
Venue: Annual Review of Cell and Developmental Biology
Publisher: Annual Reviews
Published: 2018-10-06
Volume: 34
Issue: 1
Pages: 265-288
ISSN: 1081-0706 (ISSN-L)
1530-8995
DOI: 10.1146/annurev-cellbio-100617-062653
OpenAlex: W2883831719
Cited by: 500
References: 173
Citations by year: 2026: 59 · 2025: 64 · 2024: 63 · 2023: 64 · 2022: 64 · 2021: 85 · 2020: 63 · 2019: 34 · 2018: 4
FWCI: 4.56
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Annual Review of Cell and Developmental Biology (publishedVersion)
PubMed (publishedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Institutes of Health
National Institute of General Medical Sciences (R01GM117420)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Keywords: constitutive heterochromatin, genome stability, pericentromeric heterochromatin, telomeric heterochromatin, repetitive DNA, epigenetic silencing, chromosome segregation errors, transposon activation, replication stress, aging, carcinogenesis, cancer therapy
MeSH terms: Centromere, DNA Repair, Heterochromatin, Histones, Humans, Mitosis, Repetitive Sequences, Nucleic Acid, Telomere, Genome, Chromosome Segregation, Genomic Instability

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Heterochromatin: Guardian of the Genome

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