Abstract
Double-strand breaks of DNA may lead to discontinuous DNA and consequent loss of genetic information, which may result in mutations or, ultimately, carcinogenesis. To avoid such potentially serious situations, cells have evolved efficient DNA damage repair systems. It is thought that DNA-repair processes involve drastic alterations of chromatin and histone structures, but detection of these altered structures in DNA-damaged cells remains rare in the literature. Recently, synchrotron radiation circular dichroism (SRCD) spectroscopy, which can provide secondary structural information of proteins in solution, has identified structural alterations of histone proteins induced by DNA damage responses. In this review, these results and experimental procedures are discussed with the aim of facilitating further studies of the chromatin remodeling and DNA damage repair pathways using SRCD spectroscopy.
Highlights
Nucleosomes are the basic building blocks of chromatin in eukaryotic nuclei
This information is somewhat limited compared with X-ray crystallography and nuclear magnetic resonance (NMR), both of which can be used to obtain three-dimensional structures with atomic-level resolution
circular dichroism (CD) spectroscopy is a powerful tool because it provides structural information, including structural dynamics, which is difficult for general X-ray crystallography, with the following advantages over the above techniques
Summary
Nucleosomes are the basic building blocks of chromatin in eukaryotic nuclei. The nucleosome comprises a core histone, around which 146–147 base pairs of DNA are wrapped. DSBs are harmful as they may create discontinuous DNA and a loss of genetic information, resulting in mutation or, carcinogenesis if they are not properly removed from the genome by enzymatic systems To attenuate these effects, cells have evolved DNA damage response (DDR) mechanisms, including the DSB repair pathway and cell-cycle regulation. BRCA1 binds to the polyubiquitinated histone through RAP80, and locates near the DSB site [23,24,25] Together, these events facilitate DSB repair and/or cell-cycle checkpoints. After the accumulation of repair proteins, DSB repair proceeds through two distinct mechanisms, the nonhomologous-end-joining (NHEJ) and homologous-recombination (HR) pathways [4,8,9] The former involves minimal processing of the damage by nucleases, followed by direct re-ligation of the damaged DNA ends.
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