Mutagenic bypass of uracil-derived abasic sites underlies the SBS17 mutational signature

Abstract B010: ELUCIDATING DNA DAMAGE REPAIR SIGNALING AND THERAPEUTIC VULNERABILITIES ACTIVATED BY TRANSPOSASE-DERIVED PGBD5

One hallmark of pediatric tumors is their low mutational burden, which contrasts with adult tumors, where cancer-causing mutations often accumulate over decades of DNA replication and environmental exposure. This raises the question of how such mutations arise in young patients. We have proposed that developmental mu...

Inherited DNA damage generates multi-allelic mutations in C. elegans

Exogenous and endogenous mutagens generate a wide variety of DNA lesions, including bulky adducts, chemical modifications, and single- or double-stranded breaks. A phenomenon called “lesion segregation,” in which lesions evade repair and persist for multiple cell divisions, has recently been documented in tumors and he...

Human MutLα activates methylpurine DNA glycosylase to induce alkylation damage cytotoxicity.

Alkylation chemotherapy is commonly used against tumors such as glioblastoma, yet resistance often develops through downregulation of mismatch repair (MMR). Previous work has established that loss of MMR prevents the excision of the thymine-containing strand across O 6meG-T mismatches, thereby avoiding the futile repai...

Widespread atypical UV-induced mutations form in single-stranded DNA

Persistence of common ultraviolet (UV)–induced lesions, like cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts (6-4-PPs), typically results in C>T substitutions at dipyrimidines: a mutation pattern that composes the single-base substitution (SBS) signature 7 in cancer. Oncogenic melanom...

Random (UV) Mutagenesis, Unbiased Screening and Identification of DNA Repair Mutants by Complementation Cloning.

Strain-specific outcomes of cytosine-base editing in Streptomyces

It is observed that in certain Streptomyces spp.