Molecular dynamics study on clustered DNA damage: AP sites on the same strand

Although radiation-induced clustered DNA damage can have critical biological consequences, the underlying molecular mechanisms remain unclear. To explore the effect of clustered DNA damage on DNA structure and dynamics, we performed molecular dynamics simulations on damaged DNA with two AP sites on the same strand, that is, a tandem AP cluster. The results showed that the cluster insertion of the two AP sites had a significant impact on the DNA's local and global structures. Local structural deformations as well as the extrahelical form, AP-base pairs, and irregular base pairs were frequently observed. Unlike a single AP site, the tandem AP cluster revealed that these local structural features occurred simultaneously within a small separation. Moreover, we found that the presence of tandem AP sites induced global bending of DNA. This suggests that the present case with tandem AP sites may have a non-negligible impact on the biological function of damage repair.