Transcriptional regulation and chromatin dynamics at DNA double-strand breaks

Epigenetics: How chromosome regulators orchestrate DNA repair at active genes Gene expression gets turned off in response to DNA damage thanks to a family of proteins that regulate how the genome is packaged into chromosomes. A team led by Sunwoo Min and Hyeseong Cho from Ajou University School of Medicine in Suwon, South Korea, review how the presence of DNA double-strand breaks prompts an array of genome-organizing proteins to jump into action, temporarily shutting down the process by which genes are transcribed into RNA. These proteins, known as histone modifiers and chromatin remodelers, then help coordinate the mending of broken DNA to restore genomic integrity before gene expression starts up again. A better understanding of how regulators of chromosome structure orchestrate DNA repair at active genes could lead to new therapeutic strategy for diseases such as cancer. In eukaryotic cells, DNA damage can occur at any time and at any chromatin locus, including loci at which active transcription is taking place. DNA double-strand breaks affect chromatin integrity and elicit a DNA damage response to facilitate repair of the DNA lesion. Actively transcribed genes near DNA lesions are transiently suppressed by crosstalk between DNA damage response factors and polycomb repressive complexes. Epigenetic modulation of the chromatin environment also contributes to efficient DNA damage response signaling and transcriptional repression. On the other hand, RNA transcripts produced in the G1 phase, as well as the active chromatin context of the lesion, appear to drive homologous recombination repair. Here, we discuss how the ISWI family of chromatin remodeling factors coordinates the DNA damage response and transcriptional repression, especially in transcriptionally active regions, highlighting the direct modulation of the epigenetic environment.

Automated summary

This article discusses how chromosome regulators coordinate DNA repair at active genes. Researchers have found that DNA double-strand breaks prompt a series of genome-organizing proteins to temporarily shut down the transcription of genes into RNA, and then assist in repairing the broken DNA to restore genomic integrity. A better understanding of the importance of regulating chromosome structure could lead to new therapeutic strategies for diseases such as cancer.