Dynamic DNA helps ward off gene damage - chromatin is the guardian of the genome
Edinburgh researchers have identified properties in DNA’s protective structure that could transform the way geneticists think about the human genome: June 2017
Edinburgh researchers have identified properties in DNA’s protective structure that could transform the way geneticists think about the human genome. Molecules involved in DNA’s supportive scaffolding, that were once thought to be fixed, have been found to go through dynamic and responsive changes to shield against mutations. This finding is crucial to understanding DNA damage and genome organisation and could impact current thinking on DNA-linked diseases, including cancers.
In human cells, DNA is wrapped around proteins to form chromatin. Chromatin shields the DNA from damage and regulates what genetic information can be read in a process known as transcription, where the information in a strand of DNA is copied into a new molecule of messenger RNA (mRNA). The newly formed mRNA copies of the gene then serve as blueprints for protein synthesis during the process of translation.
Researchers showed that a chemical called scaffold attachment factor A (SAF-A) binds to specific molecules known as caRNAs to form a protective chromatin mesh in a collaborative project led by the MRC Human Genetics Unit, within the IGMM and University of Edinburgh partners in Integrative Physiology and the Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot Watt University
For the first time, this mesh was shown to be dynamic, assembling and disassembling and allowing the structure to be flexible and responsive to cell signals. It was also found that the loss of SAF-A led to abnormal folding of DNA and damage to the genome.
SAF-A has previously been shown to be essential to embryo development in mouse studies and mutations of the SAF-A gene have repeatedly been found in cancer gene screening studies. This tram of Edinburgh researchers say that these findings shed light on how chromatin protects DNA from high numbers of harmful mutations, a condition known as genetic instability.
Nick Gilbert, Professor of Genetics at the University of Edinburgh’s MRC Institute of Genetics and Molecular Medicine, said: “These findings are very exciting and have fundamental implications for how we understand our own DNA, showing that chromatin is the true guardian of the genome. The results open new possibilities for investigating how we might protect against DNA mutations that we see in diseases like cancer.”
This study, published in Cell today, was carried out in collaboration with Heriot-Watt University and was funded by the Medical Research Council.
Journal Article: SAF-A regulates interphase chromosome structure through oligomerisation with chromatin-associated RNAs, Cell. 15 June 2017. DOI: 10.1016/j.cell.2017.05.029
Hear a podcast and read a transcript from The Naked Scientists, presented by Nick Gilbert - Twisting DNA.
View a video from The University of Edinburgh about our Chromatin Biology research, presented by Nick Gilbert - Packaging The Genome