A novel algorithm for the virtual screening of extensive small molecule libraries against ERCC1/XPF protein-protein interaction for the identification of resistance-bypassing potential anticancer molecules.

Background And Aim: Cancer cell's innate chemotherapeutic resistance continues to be an obstacle in molecular oncology. This theory is firmly tied to the cancer cells' integral DNA repair mechanisms continuously neutralizing the effects of chemotherapy. Amidst these mechanisms, the nuclear excision repair pathway is crucial in renovating DNA lesions prompted by agents like Cisplatin.

Protein-protein interactions in the core nucleotide excision repair pathway.

Nucleotide excision repair (NER) clears genomes of DNA adducts formed by UV light, environmental agents, and antitumor drugs. Gene mutations that lead to defects in the core NER reaction cause the skin cancer-prone disease xeroderma pigmentosum. In NER, DNA lesions are excised within an oligonucleotide of 25-30 residues via a complex, multi-step reaction that is regulated by protein-protein interactions.

Genome-wide analysis of transcription-coupled repair reveals novel transcription events in Caenorhabditis elegans.

Bulky DNA adducts such as those induced by ultraviolet light are removed from the genomes of multicellular organisms by nucleotide excision repair, which occurs through two distinct mechanisms, global repair, requiring the DNA damage recognition-factor XPC (xeroderma pigmentosum complementation group C), and transcription-coupled repair (TCR), which does not. TCR is initiated when elongating RNA polymerase II encounters DNA damage, and thus analysis of genome-wide excision repair in XPC-mutants only repairing by TCR provides a unique opportunity to map transcription events missed by methods dependent on capturing RNA transcription products and thus limited by their stability and/or modifications (5'-capping or 3'-polyadenylation). Here, we have performed eXcision Repair-sequencing (XR-seq) in the model organism Caenorhabditis elegans to generate genome-wide repair maps in a wild-type strain with normal excision repair, a strain lacking TCR (csb-1), and a strain that only repairs by TCR (xpc-1).

Correlative Analysis of ATM, RB1, ERCC2, and FANCC Mutations and Pathologic Complete Response After Neoadjuvant Chemotherapy in Patients with Muscle-invasive Bladder Cancer: Results from the SWOG S1314 Trial.

We previously reported that tumors harboring any one of four gene mutations (ATM, RB1, FANCC, or ERCC2) were likely to respond to neoadjuvant cisplatin-based chemotherapy (NAC), resulting in cancer-free surgical specimens at the time of cystectomy (pT0). Here, we report our validation of this finding. Using the CARIS 592 Gene Panel (Caris Life Sciences, Phoenix, AZ, USA), we analyzed 105 pre-NAC tumor specimens from a large multicenter trial (S1314) of either neoadjuvant gemcitabine and cisplatin (GC), or dose-dense methotrexate, vinblastine, Adriamycin, and cisplatin (DDMVAC).

Adult-Onset Neuropsychiatric Symptoms as the Presenting Feature of Xeroderma Pigmentosum Group G: A Report of a Rare Case.

Xeroderma pigmentosum is a rare autosomal recessive disorder resulting in heightened cutaneous photosensitivity due to aberrant DNA repair mechanisms. Early-life developmental delay and cognitive impairment have been described in xeroderma pigmentosum cases. However, psychiatric symptoms in adulthood as the presenting feature of xeroderma pigmentosum have not been reported.