Lesion recognition by XPC, TFIIH and XPA in DNA excision repair.

Nucleotide excision repair removes DNA lesions caused by ultraviolet light, cisplatin-like compounds and bulky adducts. After initial recognition by XPC in global genome repair or a stalled RNA polymerase in transcription-coupled repair, damaged DNA is transferred to the seven-subunit TFIIH core complex (Core7) for verification and dual incisions by the XPF and XPG nucleases. Structures capturing lesion recognition by the yeast XPC homologue Rad4 and TFIIH in transcription initiation or DNA repair have been separately reported.

Exploratory study of oxatomide derivatives with high P2X receptor inhibitory activity.

Various oxatomide derivatives were designed and synthesized to develop novel P2X receptor (P2XR) antagonists. Evaluation for in-vitro P2XR antagonist assay showed that DPM-piperazine moiety of oxatomide was required to maintain an inhibitory activity. The structure of both alkyl chains and aromatic head groups strongly affected P2XR inhibitory activity, and the analogue, with C4-type saturated alkyl chain and a non-substituted or fluorine-substituted indole, was 7.

The intrinsically disordered N-terminal region of mouse DNA polymerase alpha mediates its interaction with POT1a/b at telomeres.

Mouse telomerase and the DNA polymerase alpha-primase complex elongate the leading and lagging strands of telomeres, respectively. To elucidate the molecular mechanism of lagging strand synthesis, we investigated the interaction between DNA polymerase alpha and two paralogs of the mouse POT1 telomere-binding protein (POT1a and POT1b). Yeast two-hybrid analysis and a glutathione S-transferase pull-down assay indicated that the C-terminal region of POT1a/b binds to the intrinsically disordered N-terminal region of p180, the catalytic subunit of mouse DNA polymerase alpha.

Functional impacts of the ubiquitin-proteasome system on DNA damage recognition in global genome nucleotide excision repair.

The ubiquitin-proteasome system (UPS) plays crucial roles in regulation of various biological processes, including DNA repair. In mammalian global genome nucleotide excision repair (GG-NER), activation of the DDB2-associated ubiquitin ligase upon UV-induced DNA damage is necessary for efficient recognition of lesions. To date, however, the precise roles of UPS in GG-NER remain incompletely understood.