ID

45931

Beschrijving

Principal Investigator: Raymond J. Cho, MD, PhD, University of California, San Francisco, CA, USA MeSH: Xeroderma Pigmentosum, Complementation Group C,Carcinoma, Squamous Cell,Skin Neoplasms https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000830 Base mutations occur at higher frequencies within heterochromatin and late-replicating DNA. In this study, we show that regional differences in mutation frequency are absent in portions of the genome that are not transcribed within cutaneous squamous cell carcinomas (cSCCs) with an XPC-\- genetic background. The XPC-\- genetic background predicates a loss of global genome nucleotide excision repair (GG-NER), thus our data shows that regional differences in mutation frequency are a result of differential access of DNA repair protein. Unexpectedly, we also note that greater transcription reduces mutations on both strands of genes in heterochromatin, and only to those levels observed in euchromatin, in a XPC-dependent fashion. Therefore, transcription likely reduces mutation prevalence by increasing access to DNA repair proteins. This tripartite relationship between DNA repair, transcription, and chromatin state shows a new cancer risk factor in human populations.

Link

dbGaP study=phs000830

Trefwoorden

Versies (1)

1. 09-03-24 09-03-24 - Madita Rudolph

Houder van rechten

Raymond J. Cho, MD, PhD, University of California, San Francisco, CA, USA

Geüploaded op

9 maart 2024

DOI

Voor een aanvraag inloggen.

Licentie