Exploring plasma DNA fragmentation

Short fragments of DNA circulating in plasma can be analyzed for cancer diagnosis and prenatal testing, but the mechanisms by which plasma DNA is fragmented are unclear.

Researchers found that loss of the secreted nuclease DNase1-like 3 (DNASE1L3) resulted in the aberrant fragmentation of plasma DNA. Loss of Dnase1L3 was associated with an increase in plasma DNA molecules above 250 bp and below 120 bp in size, and the latter were positively correlated with anti-DNA antibody levels.

The results suggest that the increase in relatively long DNA fragments may be a primary effect of DNASE1L3 deficiency, whereas the increase in short DNA fragments may be the result of the anti-DNA response.

DNASE1L3 loss also caused a decrease in frequencies of the most common plasma DNA end sequence motifs. In Dnase1l3 knockout mice pregnant with fetuses heterozygous for Dnase1l3, the authors found partial restoration of normal frequencies of plasma DNA end motifs, suggesting that DNASE1L3 from fetuses had a systemic effect on maternal plasma DNA in addition to a local effect on fetal DNA.

According to the authors, DNASE1L3 plays a role in the fragmentation of circulating plasma DNA, and exploring plasma DNA fragmentation could help improve molecular diagnostics and reveal how DNASE1L3 prevents autoimmunity.