Heterochromatin: Guardian of the Genome

被引：325

作者：

Janssen, Aniek ^{[1
,2
]}

Colmenares, Serafin U. ^{[1
,2
]}

Karpen, Gary H. ^{[1
,2
]}

机构：

[1] Lawrence Berkeley Natl Lab, Biol Syst & Engn Div, Berkeley, CA 94720 USA

[2] Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA

来源：

ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 34 | 2018年 / 34卷

关键词：

constitutive heterochromatin; pericentromeres; genome stability; chromosome segregation; repetitive DNA; DNA repair; REGIONAL MUTATION-RATES; DNA MISMATCH REPAIR; HISTONE H3; PERICENTRIC HETEROCHROMATIN; TRANSPOSABLE ELEMENTS; HP1; PROTEINS; CHROMATIN ORGANIZATION; L1; RETROTRANSPOSITION; EPIGENETIC REGULATION; LYSINE-9; METHYLATION;

D O I：

10.1146/annurev-cellbio-100617-062653

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：265 / 288

页数：24

共 171 条

[1] Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3-9 encode centromere-associated proteins which complex with the heterochromatin component M31 [J].