Myc-driven chromatin accessibility regulates Cdc45 assembly into CMG helicases

Autor:	Victoria L. Bryant, Brook S. Nepon-Sixt, Mark G. Alexandrow
Jazyk:	angličtina
Rok vydání:	2019
Předmět:	DNA Replication Genes myc Medicine (miscellaneous) Cell Cycle Proteins Plasma protein binding CHO Cells Origin of replication medicine.disease_cause General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences 0302 clinical medicine Cricetulus medicine Animals Humans p300-CBP Transcription Factors Gene lcsh:QH301-705.5 030304 developmental biology 0303 health sciences biology DNA replication DNA Helicases Helicase Chromatin Assembly and Disassembly GINS Chromatin 3. Good health Cell biology Enzyme Activation lcsh:Biology (General) 030220 oncology & carcinogenesis biology.protein General Agricultural and Biological Sciences Carcinogenesis Biomarkers Protein Binding
Zdroj:	Communications Biology, Vol 2, Iss 1, Pp 1-15 (2019) Communications Biology
ISSN:	2399-3642
DOI:	10.1038/s42003-019-0353-2
Popis:	Myc-driven tumorigenesis involves a non-transcriptional role for Myc in over-activating replication origins. We show here that the mechanism underlying this process involves a direct role for Myc in activation of Cdc45-MCM-GINS (CMG) helicases at Myc-targeted sites. Myc induces decondensation of higher-order chromatin at targeted sites and is required for chromatin access at a chromosomal origin. Myc-driven chromatin accessibility promotes Cdc45/GINS recruitment to resident MCMs, and activation of CMGs. Myc-Box II, which is necessary for Myc-driven transformation, is required for Myc-induced chromatin accessibility, Cdc45/GINS recruitment, and replication stimulation. Myc interactors GCN5, Tip60, and TRRAP are essential for chromatin unfolding and recruitment of Cdc45, and co-expression of GCN5 or Tip60 with MBII-deficient Myc rescues these events and promotes CMG activation. Finally, Myc and Cdc45 interact and physiologic conditions for CMG assembly require the functions of Myc, MBII, and GCN5 for Cdc45 recruitment and initiation of DNA replication. Nepon-Sixt, Bryant, and Alexandrow show that Myc increases the chromatin accessibility through Myc-Box II, activating Cdc45-MCM-GINS helicases at Myc-targeted sites. This study highlights a non-transcriptional role for Myc in over-activating DNA replication, providing insight into Myc-driven tumorigenesis.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::94e3923dd0f06c753fbf70153fead97b http://link.springer.com/article/10.1038/s42003-019-0353-2 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.