Breakage of cytoplasmic chromosomes by pathological DNA base excision repair.

ABSTRACT: Chromothripsis is a catastrophic mutational process that promotes tumorigenesis and causes congenital disease^1-4. Chromothripsis originates from aberrations of nuclei called micronuclei or chromosome bridges^5-8. These structures are associated with fragile nuclear envelopes that spontaneously rupture^9,10, leading to DNA damage when chromatin is exposed to the interphase cytoplasm. Here we identify a mechanism explaining a major fraction of this DNA damage. Micronuclei accumulate large amounts of RNA-DNA hybrids, which are edited by adenine deaminases acting on RNA (ADAR enzymes) to generate deoxyinosine. Deoxyinosine is then converted into abasic sites by a DNA base excision repair (BER) glycosylase, N-methyl-purine DNA glycosylase^11,12 (MPG). Th

SUBMITTER: Tang S 

PROVIDER: S-EPMC10680091 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature