LUMC researchers identify important new proteins for DNA repair in chromatin13 November 2020• NEWSITEM
Researchers from the department of Human Genetics of the Leiden University Medical Center (LUMC) have identified new proteins that facilitate repair of DNA damage by opening and closing chromatin, which is the packaging material of our DNA. Their findings have been published in the prestigious journal Nature Communications.
Each cell of our body contains approximately two meters of DNA if stretched out. This DNA is tightly packaged with proteins into a structure called chromatin. Despite being packaged, chromatin is sufficiently flexible to allow DNA-based processes, such as the repair of DNA damage, to occur.
The lab of Haico van Attikum, professor of Chromatin and DNA repair, has been working for years on understanding how damaged DNA is repaired in chromatin. “Our DNA becomes damaged on a daily basis. DNA double-strand breaks are among the most detrimental types of DNA damage, which, if left unrepaired or repaired incorrectly, may lead to genome instability and diseases such as cancer”, explains Van Attikum.
“To repair DNA breaks, the chromatin has to somehow open up so repair proteins can access the break and do their work. After the repair process has been completed, chromatin has to be closed again.” How these dynamic changes in chromatin that occur during DNA repair are regulated is largely unknown.
Magda Rother, a senior researcher in Van Attikum’s team, has identified the Chromodomain Helicase DNA Binding Protein 7 (CHD7) as a new protein involved in the repair of DNA double-strand breaks. “We found that CHD7 is recruited when a DNA double-strand break occurs. Subsequently, it locally opens up the chromatin to attract repair proteins. Soon after repair, CHD7 also helps to close the chromatin”, says Rother.
Van Attikum: “We were surprised to find that CHD7 is involved in seemingly opposing activities, namely the opening and closing of chromatin.” This puzzle was, however, resolved by showing that CHD7 opens chromatin through its enzymatic activity, while recruiting other enzymes that close chromatin by chemical modification.
CHD7 is often mutated in patients with CHARGE syndrome. “We want to find out whether certain clinical manifestations, particularly the immunodeficiency, associated with this syndrome can be explained by the loss of CHD7-dependent repair activities”, says Van Attikum.
Read the article ‘CHD7 and 53BP1 regulate distinct pathways for the re-ligation of DNA double-strand breaks’ here.