Replication stress, a source of epigenetic aberrations in cancer?
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Replication stress, a source of epigenetic aberrations in cancer? / Jasencakova, Zusana; Groth, Anja.
In: BioEssays, Vol. 32, No. 10, 10.2010, p. 847-55.Research output: Contribution to journal › Review › Research › peer-review
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TY - JOUR
T1 - Replication stress, a source of epigenetic aberrations in cancer?
AU - Jasencakova, Zusana
AU - Groth, Anja
PY - 2010/10
Y1 - 2010/10
N2 - 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.
AB - 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.
U2 - 10.1002/bies.201000055
DO - 10.1002/bies.201000055
M3 - Review
C2 - 20726011
VL - 32
SP - 847
EP - 855
JO - BioEssays
JF - BioEssays
SN - 0265-9247
IS - 10
ER -
ID: 21661572