{"id":29338,"date":"2020-06-24T17:23:36","date_gmt":"2020-06-24T15:23:36","guid":{"rendered":"https:\/\/www.embl.org\/news\/?p=29338"},"modified":"2024-03-22T13:21:46","modified_gmt":"2024-03-22T12:21:46","slug":"unpicking-the-complexity-of-dna-mutations","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/unpicking-the-complexity-of-dna-mutations\/","title":{"rendered":"Unpicking the complexity of DNA mutations"},"content":{"rendered":"\n

Tobacco smoke, UV radiation, and certain chemicals are some of the factors that can damage the genetic material of cells, triggering cancer. These factors modify individual letters in the DNA code, called nucleotides. When a cell divides, some of these errors \u2013 or lesions \u2013 are resolved by a mechanism called DNA repair, but others remain unrepaired and become permanent changes in the DNA, known as mutations. This can result in health problems, such as cancer. Such mutational processes are extremely complex and there are still many unanswered questions about how they work.<\/p>\n\n\n\n

A new study led by the University of Cambridge and the University of Edinburgh, and supported by EMBL’s European Bioinformatics Institute (EMBL-EBI)<\/a>, has examined the evolution of tumours in mice following chemical damage. The research, published in the journal Nature<\/em><\/a>, shows that DNA lesions caused by chemical damage are not eliminated immediately, but are passed on unrepaired through several rounds of cell division.<\/p>\n\n\n\n

Lesion segregation<\/strong><\/h3>\n\n\n\n

The researchers also found that, during cell division, the two DNA strands \u2013 each with its own set of lesions and mutations, are separated into two daughter cells with different patterns of DNA changes. During further rounds of replication, the lesions repeatedly generate new combinations of mutations. This phenomenon, called lesion segregation, can result in extremely complex patterns of mutations in a tumour\u2019s genome.<\/p>\n\n\n\n

The researchers used the DNA-damaging chemical diethylnitrosamine to induce liver tumours in mice, and then analysed the tumour genomes.<\/p>\n\n\n\n

\u201cPersistent DNA lesions induced by chemotherapeutic agents segregate and produce several generations of further mutations. We need to be aware of this therapeutically, and in future drug development,” says Martin Taylor from the University of Edinburgh\u2019s MRC Human Genetics Unit.<\/p>\n\n\n\n

A model for mutational processes<\/strong><\/h3>\n\n\n\n

\u201cThese new insights into how mutational processes work are interesting and unexpected,\u201d says Paul Flicek, Associate Director of EMBL-EBI Services. \u201cThe idea that DNA lesions are not resolved within a cell cycle and stay around for a long time is an important one. It shows that cells can evolve faster than the machinery can fix them and this has implications for how we think about cancer.\u201d<\/p>\n\n\n\n

Find out more about the study:<\/strong><\/p>\n\n\n\n