Histone dynamics during DNA replication stress

Abstract

Accurate and complete replication of the genome is essential not only for genome stability but also for cell viability. However, cells face constant threats to the replication process, such as spontaneous DNA modifications and DNA lesions from endogenous and external sources. Any obstacle that slows down replication forks or perturbs replication dynamics is generally considered to be a form of replication stress, and the past decade has seen numerous advances in our understanding of how cells respond to and resolve such challenges. Furthermore, recent studies have also uncovered links between defects in replication stress responses and genome instability or various diseases, such as cancer. Because replication stress takes place in the context of chromatin, histone dynamics play key roles in modulating fork progression and replication stress responses. Here, we summarize the current understanding of histone dynamics in replication stress, highlighting recent advances in the characterization of fork-protective mechanisms.

Changes in Epigenetic Patterns Related to DNA Replication in Vicia faba Root Meristem Cells under Cadmium-Induced Stress Conditions

“…Currently, we define RS as slowing down or stopping the movement of replication forks and/or DNA synthesis. Since DNA synthesis, as well as the cellular response to RS, occur in the context of chromatin, histone dynamics play a key role in modulating fork progression [ 7 , 8 ]. It is known that DNA replication requires simultaneous separation and reassembly of chromatin, and prolonged disruption and/or inhibition of replication carries a high risk of altering the newly formed chromatin in a way that may alter epigenetic information; these, in turn, may affect gene regulation and the spatial organization of DNA [ 9 ].…”

Anti-Cancer Mechanisms of Diarylpentanoid MS17 (1,5-Bis(2-hydroxyphenyl)-1,4-pentadiene-3-one) in Human Colon Cancer Cells: A Proteomics Approach

“…Histone H1-3 overexpression in epithelial ovarian cancer cells has been reported to reduce cell proliferation and colony formation by suppressing the noncoding oncogene H19 [ 217 ]. Histones H1-2 and H1-3 were downregulated in MS17-treated SW620 cells and significantly associated with “Cellular responses to stress.” Under cellular stress, histone H1 can undergo various modifications, such as acetylation, phosphorylation, methylation, and ubiquitination, which affect its interaction with DNA and other proteins [ 218 , 219 ]. These modifications can alter the chromatin dynamics and the transcriptional stress response [ 219 , 220 , 221 , 222 ].…”

“…Histones H1-2 and H1-3 were downregulated in MS17-treated SW620 cells and significantly associated with “Cellular responses to stress.” Under cellular stress, histone H1 can undergo various modifications, such as acetylation, phosphorylation, methylation, and ubiquitination, which affect its interaction with DNA and other proteins [ 218 , 219 ]. These modifications can alter the chromatin dynamics and the transcriptional stress response [ 219 , 220 , 221 , 222 ]. For example, histone H1 acetylation can reduce its affinity for DNA and increase the accessibility of stress-responsive genes [ 223 ].…”

Epigenetic modifications evidenced by isolation of proteins on nascent DNA and immunofluorescence in hydroxyurea-treated root meristem cells of Vicia faba

“…The process of DNA replication requires both the dissociation of histones, separation of DNA strands and an integrated way of reassembling chromatin on the two DNA duplexes. Since both DNA replication and cellular response to replication stress (RS) occur in the context of chromatin, histone dynamics as well as functioning of proteins involved in the induction and progression of nuclear replication play a key roles in modulating replication forks (RFs) progression (Hsu et al 2014 ; Zeman and Cimprich 2014 ). Prolonged disruption and/or inhibition of replication carries a high risk of altering newly formed chromatin in ways that can modify epigenetic information, affect the spatial organization of DNA and deregulate gene expression (Khurana and Oberdoerffer 2015 ).…”