Radiation-induced alterations in histone modification patterns and their potential impact on short-term radiation effects

Anna A Friedl,Belinda Mazurek,Doris M Seiler

doi:10.3389/fonc.2012.00117

Abstract

Detection and repair of radiation-induced DNA damage occur in the context of chromatin. An intricate network of mechanisms defines chromatin structure, including DNA methylation, incorporation of histone variants, histone modifications, and chromatin remodeling. In the last years it became clear that the cellular response to radiation-induced DNA damage involves all of these mechanisms. Here we focus on the current knowledge on radiation-induced alterations in post-translational histone modification patterns and their effect on the chromatin accessibility, transcriptional regulation and chromosomal stability.

Highlights

The genetic information is stored in the DNA, which in eukaryotes is organized in chromosomes
A picture emerges that transcriptional repression at γ-H2AX domains is associated with a loss of S5- and S2-phosphorylated RNA Polymerase II (RNAPII), but not with a loss of total RNAPII. This is in contrast to mechanisms described for transcriptional inhibition after induction of bulky DNA lesions, such as for example induced by UV irradiation, where RNA polymerase stalls at the damaged site and is removed by proteosomal degradation after K48-linked ubiquitination (Heine et al, 2008; Hammond-Martel et al, 2012) in a process accompanied by hyperphosphorylation of the C-terminal domain (CTD), especially at S5
Immunofluorescence analysis after double-strand breaks (DSBs) induction by ionizing radiation, coupled with elaborate image analysis methods including ultra-thin sectioning of cells, demonstrated a loss of H3K4me3 and H3K4me2 signals in the γ H2AX domains, which started within minutes after damage infliction and increased over time (Seiler et al, 2011)

Summary

Introduction

The genetic information is stored in the DNA, which in eukaryotes is organized in chromosomes. In addition to DSB induction by ionizing radiation or DSB-inducing chemical agents, such as neocarcinostatin, many IF-based studies used laser microirradiation to investigate PTM patterns at damage sites.

Results

Conclusion