Universität zu Köln

Franz, Andre, Pirson, Paul A., Pilger, Domenic ORCID: 0000-0001-7339-0685, Halder, Swagata, Achuthankutty, Divya, Kashkar, Hamid, Ramadan, Kristijan and Hoppe, Thorsten ORCID: 0000-0002-4734-9352 (2016). Chromatin-associated degradation is defined by UBXN-3/FAF1 to safeguard DNA replication fork progression. Nat. Commun., 7. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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Abstract

The coordinated activity of DNA replication factors is a highly dynamic process that involves ubiquitin-dependent regulation. In this context, the ubiquitin-directed ATPase CDC-48/p97 recently emerged as a key regulator of chromatin-associated degradation in several of the DNA metabolic pathways that assure genome integrity. However, the spatiotemporal control of distinct CDC-48/p97 substrates in the chromatin environment remained unclear. Here, we report that progression of the DNA replication fork is coordinated by UBXN-3/FAF1. UBXN-3/FAF1 binds to the licensing factor CDT-1 and additional ubiquitylated proteins, thus promoting CDC-48/p97-dependent turnover and disassembly of DNA replication factor complexes. Consequently, inactivation of UBXN-3/FAF1 stabilizes CDT-1 and CDC-45/GINS on chromatin, causing severe defects in replication fork dynamics accompanied by pronounced replication stress and eventually resulting in genome instability. Our work identifies a critical substrate selection module of CDC-48/p97 required for chromatinassociated protein degradation in both Caenorhabditis elegans and humans, which is relevant to oncogenesis and aging.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Franz, Andre UNSPECIFIED UNSPECIFIED UNSPECIFIED Pirson, Paul A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pilger, Domenic UNSPECIFIED orcid.org/0000-0001-7339-0685 UNSPECIFIED Halder, Swagata UNSPECIFIED UNSPECIFIED UNSPECIFIED Achuthankutty, Divya UNSPECIFIED UNSPECIFIED UNSPECIFIED Kashkar, Hamid UNSPECIFIED UNSPECIFIED UNSPECIFIED Ramadan, Kristijan UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoppe, Thorsten UNSPECIFIED orcid.org/0000-0002-4734-9352 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-285262
DOI:	10.1038/ncomms10612
Journal or Publication Title:	Nat. Commun.
Volume:	7
Date:	2016
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2041-1723
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CAENORHABDITIS-ELEGANS EMBRYOS; AAA-ATPASE; CELL-CYCLE; S-PHASE; CHROMOSOMAL INSTABILITY; PROTEIN-DEGRADATION; GENOMIC INSTABILITY; MCM2-7 HELICASE; COMPLEX; DAMAGE Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28526