N 2-Alkyl-dG lesions elicit R-loop accumulation in the genome.

Humans are exposed to DNA alkylating agents through endogenous metabolism, environmental exposure and cancer chemotherapy. The resulting alkylated DNA adducts may elicit genome instability by perturbing DNA replication and transcription. R-loops regulate various cellular processes, including transcription, DNA repair, and telomere maintenance.

HMGB3 and SUB1 Bind to and Facilitate the Repair of -Alkylguanine Lesions in DNA.

-Alkyl-2'-deoxyguanosine (-alkyl-dG) is a major type of minor-groove DNA lesions arising from endogenous metabolic processes and exogenous exposure to environmental contaminants. The -alkyl-dG lesions, if left unrepaired, can block DNA replication and transcription and induce mutations in these processes. Nevertheless, the repair pathways for -alkyl-dG lesions remain incompletely elucidated.

DNA polymerase κ participates in early S-phase DNA replication in human cells.

Cycling cells replicate their DNA during the S phase through a defined temporal program known as replication timing. Mutation frequencies, epigenetic chromatin states, and transcriptional activities are different for genomic regions that are replicated early and late in the S phase. Here, we found from ChIP-Seq analysis that DNA polymerase (Pol) κ is enriched in early-replicating genomic regions in HEK293T cells.

The aflatoxin B-induced imidazole ring-opened guanine adduct: High mutagenic potential that is minimally affected by sequence context.

Dietary exposure to aflatoxin B (AFB) is a recognized risk factor for developing hepatocellular carcinoma. The mutational signature of AFB is characterized by high-frequency base substitutions, predominantly G>T transversions, in a limited subset of trinucleotide sequences. The 8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)-9-hydroxyaflatoxin B (AFB-FapyGua) has been implicated as the primary DNA lesion responsible for AFB-induced mutations.

Base excision repair of the N-(2-deoxy-d-erythro-pentofuranosyl)-urea lesion by the hNEIL1 glycosylase.

The N-(2-deoxy-d-erythro-pentofuranosyl)-urea DNA lesion forms following hydrolytic fragmentation of cis-5R,6S- and trans-5R,6R-dihydroxy-5,6-dihydrothymidine (thymine glycol, Tg) or from oxidation of 7,8-dihydro-8-oxo-deoxyguanosine (8-oxodG) and subsequent hydrolysis. It interconverts between α and β deoxyribose anomers. Synthetic oligodeoxynucleotides containing this adduct are efficiently incised by unedited (K242) and edited (R242) forms of the hNEIL1 glycosylase.