Clues to quality of journals
Open Access Policy of Helmholtz Association 2016
CC Licencences
Publication Metrics
Home
Deutsch
New EVA Application
Advanced Search
Browse by ...
Publication overview
Statistics (last 5 years)
OA Publications
Submit Publication
Import publication from...
Report missing publication
Contact persons
Help
Text
Endnote (RIS)
BibTeX
Publ. Version/Full Text
Research data
DOI
PMC
 |
Open Access Gold |
|
as soon as is submitted to ZB.
The Cdk8/19-cyclin C transcription regulator functions in genome replication through metazoan Sld7.
PLoS Biol. 17:e2006767 (2019)
Accurate genome duplication underlies genetic homeostasis. Metazoan Mdm2 binding protein (MTBP) forms a main regulatory platform for origin, firing together with Topoisomerase II binding protein 1 (TopBP1)-interacting replication stimulating protein/TopBP1-interacting checkpoint and replication regulator (Treslin/TICRR) and TopBP1. We report the first comprehensive analysis of MTBP and reveal conserved and metazoa-specific MTBP functions in replication. This suggests that metazoa have evolved specific molecular mechanisms to adapt replication principles conserved with yeast to the specific requirements of the more complex metazoan cells. We uncover one such metazoa-specific process: a new replication factor, cyclin-dependent kinase 8/19-cyclinC (Cdk8/19-cyclin C), binds to a central domain of MTBP. This interaction is required for complete genome duplication in human cells. In the absence of MTBP binding to Cdk8/19-cyclin C, cells enter mitosis with incompletely duplicated chromosomes, and subsequent chromosome segregation occurs inaccurately. Using remote homology searches, we identified MTBP as the metazoan orthologue of yeast synthetic lethal with Dpb11 7 (Sld7). This homology finally demonstrates that the set of yeast core factors sufficient for replication initiation in vitro is conserved in metazoa. MTBP and Sld7 contain two homologous domains that are present in no other protein, one each in the N and C termini. In MTBP the conserved termini flank the metazoa-specific Cdk8/19-cyclin C binding region and are required for normal origin firing in human cells. The N termini of MTBP and Sld7 share an essential origin firing function, the interaction with Treslin/TICRR or its yeast orthologue Sld3, respectively. The C termini may function as homodimerisation domains. Our characterisation of broadly conserved and metazoa-specific initiation processes sets the basis for further mechanistic dissection of replication initiation in vertebrates. It is a first step in understanding the distinctions of origin firing in higher eukaryotes.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Times Cited
Scopus
Cited By
Cited By
Altmetric
8.386
2.040
15
19
Annotations
Special Publikation
Hide on homepage
Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Cdk-dependent Phosphorylation; Promotes Dna-replication; Initiation; Complex; Checkpoint; Origins; Helicase; Treslin; Binding; Kinase
Language
english
Publication Year
2019
HGF-reported in Year
2019
ISSN (print) / ISBN
1544-9173
e-ISSN
1545-7885
Journal
PLoS Biology
Quellenangaben
Volume: 17,
Issue: 1,
Article Number: e2006767
Publisher
Public Library of Science (PLoS)
Publishing Place
1160 Battery Street, Ste 100, San Francisco, Ca 94111 Usa
Reviewing status
Peer reviewed
Institute(s)
CF Monoclonal Antibodies (CF-MAB)
Research Unit Gene Vector (AGV)
Research Unit Gene Vector (AGV)
POF-Topic(s)
30201 - Metabolic Health
30203 - Molecular Targets and Therapies
30203 - Molecular Targets and Therapies
Research field(s)
Helmholtz Diabetes Center
Immune Response and Infection
Immune Response and Infection
PSP Element(s)
G-502210-001
G-501500-004
G-501500-004
WOS ID
WOS:000457596000007
Scopus ID
85061480005
PubMed ID
30695077
Erfassungsdatum
2019-03-12