Endogenous DNA damage at sites of terminated transcripts.

ABSTRACT: DNA damage promotes mutations that fuel cancer, ageing and neurodegenerative diseases^1-3, but surprisingly, the causes and types of damage remain largely unknown. There are three identified mechanisms that damage DNA during transcription: collision of RNA polymerase (RNAP) with the DNA-replication machinery head-on and co-directionally^4-6, and R-loop-induced DNA breakage^7-10. Here we identify novel DNA damage reaction intermediates^11,12 and uncover a fourth transcription-related source of DNA damage: endogenous DNA damage at sites of terminated transcripts. We engineered proteins to capture single-stranded DNA (ssDNA) ends with 3' polarity in bacterial and human cells. In Escherichia coli, spontaneous 3'-ssDNA-end foci were unexpectedly frequent,

SUBMITTER: Liu J 

PROVIDER: S-EPMC12629516 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature