Epigenetic Regulation of Genome Integrity and its Implications in Human Diseases

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Background

The human genome is constantly challenged by both endogenous and exogenous sources of genotoxic stress, such as reactive oxidative species from metabolic activities, ultraviolet (UV), ionizing radiation (IR), and other DNA damaging chemicals. If not resolved properly, these DNA lesions can cause a wide range of adverse effects, including replication stress, transcription de-regulation, genetic mutations and chromosome aberrations, which can eventually lead to cell death and contribute to human diseases. In actively proliferating cells, genome integrity is preserved through a highly coordinated regulatory network, which ensures faithful DNA replication during S phase, accurate chromosome segregation in mitosis, and error-free repair of DNA damage throughout the cell cycle. Importantly, epigenetic factors have been shown to play crucial roles in the processes. During DNA replication, both parental and newly-synthesized histones are incorporated into the nascent chromatin by a dedicated group of histone chaperones, a key step for the re-establishment of a functional epigenome in daughter cells. In mitosis, the centromere is subjected to extensive epigenetic rewiring to reorganize local chromatin environment and mediate the precise separation of sister chromatids. By altering nucleosome accessibility or providing docking sites, certain histone marks can recruit DNA damage response proteins to facilitate DNA repair at different stages.


While significant progresses have been made in the related fields, many critical questions remain unanswered, especially when it comes to novel epigenetic factors and mechanisms. Therefore, we’re launching this research topic in an effort to advance the mechanistic understandings of the epigenetic regulation of genome integrity under both normal and pathological conditions. To bridge the gap between basic and translational research, we also welcome studies that target such mechanisms as therapeutic opportunities in cancer and other diseases, in which evidence of epigenetic regulation are emerging. Both original research and review articles that fall in the scope of this topic are welcomed. However, all original research articles submitted to this collection should have significant experimental validation and studies consisting of solely bioinformatic investigation or theoretical analysis of publicly available datasets will not be considered.

The research topics include, but are not limited to the following:

- The roles of histone chaperones in genome stability and human diseases
- Epigenetic regulation of chromosome segregation
- Epigenetic regulation of DNA damage response and repair
- Epigenetic regulation of cellular responses to DNA replication stress

Keywords: genome integrity

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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