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Replication stress, a source of epigenetic aberrations in cancer?
Author(s) -
Jasencakova Zuzana,
Groth Anja
Publication year - 2010
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.201000055
Subject(s) - chromatin , epigenetics , biology , histone , genome instability , genetics , cancer epigenetics , histone code , chromatin remodeling , microbiology and biotechnology , dna replication , epigenome , dna methylation , histone methyltransferase , dna damage , nucleosome , dna , gene , gene expression
Cancer cells accumulate widespread local and global chromatin changes and the source of this instability remains a key question. Here we hypothesize that chromatin alterations including unscheduled silencing can arise as a consequence of perturbed histone dynamics in response to replication stress. Chromatin organization is transiently disrupted during DNA replication and maintenance of epigenetic information thus relies on faithful restoration of chromatin on the new daughter strands. Acute replication stress challenges proper chromatin restoration by deregulating histone H3 lysine 9 mono‐methylation on new histones and impairing parental histone recycling. This could facilitate stochastic epigenetic silencing by laying down repressive histone marks at sites of fork stalling. Deregulation of replication in response to oncogenes and other tumor‐promoting insults is recognized as a significant source of genome instability in cancer. We propose that replication stress not only presents a threat to genome stability, but also jeopardizes chromatin integrity and increases epigenetic plasticity during tumorigenesis.