About this Research Topic
The integrity of the genome is continuously challenged by endogenous and exogenous DNA damaging agents and by lesions arising during DNA replication. To prevent the severe biological consequences that may arise from DNA injuries, cells have evolved an intricate network of genome surveillance mechanisms, collectively designated as DNA damage response (DDR). In addition to damage-specific repair machineries, perturbations in the structure and continuity of the DNA molecule trigger checkpoint pathways that delay or arrest cell-cycle progression thus providing more time for repair mechanisms. Moreover, checkpoint pathways coordinate DNA repair with DNA replication and transcription. Functional alterations in any of these processes and in their crosstalk may result in uncontrolled cell proliferation or programmed cell death, two opposite events that are harmful both at the cellular and organismal level.
In eukaryotic cells, DNA is packaged into chromatin that is the substrate of all DNA transactions. Changes in chromatin architecture induced by reversible histone post-translational modifications (PTMs), incorporation of histone variants and ATP-dependent chromatin remodeling enzymes, occur in response to external and cellular cues and affect vital processes such as regulation of gene expression, DNA replication and repair. Histone modifications are best understood for their effects on transcription, but it is becoming increasingly evident that they also function in the DDR, where chromatin reorganization is required to allow access of repair proteins to DNA lesions. While some histone modifications, such as phosphorylation of histone variant H2AX and ubiquitylation of histone H2A, are unique to the DDR others are involved both in transcription and DNA repair. However, we are still far from a clear and comprehensive picture of histone PTMs in relation to DDR. Finally, recent data implicate splicing factors, small non-coding RNAs and components of the RNA interference machinery in chromatin organization both in unstressed cells and in response to DNA damage.
The objective of this Research Topic is to provide a comprehensive view of the complex network of interactions that contribute to the DNA damage response and genome stability in eukaryotes through modulation of the chromatin structure. Special emphasis will be given to the emerging crosstalk between non-coding RNAs, chromatin and transcription/pre-mRNA processing in the context of DNA damage.
In eukaryotic cells, DNA is packaged into chromatin that is the substrate of all DNA transactions. Changes in chromatin architecture induced by reversible histone post-translational modifications (PTMs), incorporation of histone variants and ATP-dependent chromatin remodeling enzymes, occur in response to external and cellular cues and affect vital processes such as regulation of gene expression, DNA replication and repair. Histone modifications are best understood for their effects on transcription, but it is becoming increasingly evident that they also function in the DDR, where chromatin reorganization is required to allow access of repair proteins to DNA lesions. While some histone modifications, such as phosphorylation of histone variant H2AX and ubiquitylation of histone H2A, are unique to the DDR others are involved both in transcription and DNA repair. However, we are still far from a clear and comprehensive picture of histone PTMs in relation to DDR. Finally, recent data implicate splicing factors, small non-coding RNAs and components of the RNA interference machinery in chromatin organization both in unstressed cells and in response to DNA damage.
The objective of this Research Topic is to provide a comprehensive view of the complex network of interactions that contribute to the DNA damage response and genome stability in eukaryotes through modulation of the chromatin structure. Special emphasis will be given to the emerging crosstalk between non-coding RNAs, chromatin and transcription/pre-mRNA processing in the context of DNA damage.
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