Lack of DNA2 nuclease leads to frequent insertion of complex DNA fragments at chromosome breaks

Lack of DNA2 nuclease leads to frequent insertion of complex DNA fragments at chromosome breaks

December 19, 2018 Source: Ministry of Science and Technology

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On December 5th, researchers such as Baylor College of Medicine and Cornell University published an article entitled "Dna2 nuclease deficiency results in large and complex DNA insertions at chromosomal breaks" on Nature, through yeast lacking Dna2 nuclease. Studies of mutant strains revealed that Dna2 nuclease deficiency caused frequent insertion of large and complex DNA fragments at the chromosomal break, disrupting chromosome stability.

Insertion of mobile elements, mitochondrial DNA, and nuclear chromosomal fragments at DNA double-strand breaks (DSBs) threatens genomic integrity and is common in cancer. Insertion of a chromosomal fragment into the V(D)J recombination site facilitates the production of diverse antibodies, and the initiation of chromosomal fragment insertion and the mechanism by which such insertion is prevented are still unclear. In the present study, the researchers found that when yeast lacks the evolutionarily conserved Dna2 nuclease, the mutant showed frequent insertions of about 0.1-1.5 kb in length at DSBs, including many linked by multiple DNA fragments. the sequence of. Sequencing of about 500 DNA inserts revealed that 8% of these sequences were derived from Ty transposons, 15% were derived from ribosomal DNA (rDNA), and the rest were derived from the entire genome, mainly the origin of replication, R-ring, Fragile areas such as filaments, telomeres or replication fork barriers. Since the insert is not lost at its original location, there are many repetitions. These repeats depend on non-homologous end joining (NHEJ) and POL4. The researchers predict that as long as any cell has a linear extrachromosomal DNA fragment, DNA insertion at similar DSBs is likely to occur. The study provides a new therapeutic strategy for cancer patients who lack the components of the innate immune system responsible for clearing foreign DNA. (Excerpt from Nature, Published: 05 December 2018)

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