Defective Hfp-dependent transcriptional repression of dMYC is fundamental to tissue overgrowth in Drosophila XPB models
Date
2015
Authors
Lee, Jue Er Amanda
Mitchell, Naomi
Zaytseva, Olga
Chahal, Arjun
Mendis, Peter
Cartier-Michaud, Amandine
Parsons, Linda M.
Poortinga, Gretchen
Levens, David
Hannan, Ross
Journal Title
Journal ISSN
Volume Title
Publisher
Macmillan Publishers Ltd
Abstract
Nucleotide excision DNA repair (NER) pathway mutations cause neurodegenerative and progeroid disorders (xeroderma pigmentosum (XP), Cockayne syndrome (CS) and trichothiodystrophy (TTD)), which are inexplicably associated with (XP) or without (CS/TTD) cancer. Moreover, cancer progression occurs in certain patients, but not others, with similar C-terminal mutations in the XPB helicase subunit of transcription and NER factor TFIIH. Mechanisms driving overproliferation and, therefore, cancer associated with XPB mutations are currently unknown. Here using Drosophila models, we provide evidence that C-terminally truncated Hay/XPB alleles enhance overgrowth dependent on reduced abundance of RNA recognition motif protein Hfp/FIR, which transcriptionally represses the MYC oncogene homologue, dMYC. The data demonstrate that dMYC repression and dMYC-dependent overgrowth in the Hfp hypomorph is further impaired in the C-terminal Hay/XPB mutant background. Thus, we predict defective transcriptional repression of MYC by the Hfp orthologue, FIR, might provide one mechanism for cancer progression in XP/CS
Description
Keywords
Citation
Collections
Source
Nature Communications
Type
Journal article
Book Title
Entity type
Access Statement
Open Access
License Rights
Restricted until
Downloads
File
Description