PUBLICATION

Resting cells rely on the DNA helicase component MCM2 to build cilia

Authors
Casar Tena, T., Maerz, L.D., Szafranski, K., Groth, M., Blätte, T.J., Donow, C., Matysik, S., Walther, P., Jeggo, P.A., Burkhalter, M.D., Philipp, M.
ID
ZDB-PUB-181018-8
Date
2018
Source
Nucleic acids research   47(1): 134-151 (Journal)
Registered Authors
Burkhalter, Martin, Philipp, Melanie
Keywords
none
MeSH Terms
  • Animals
  • Cilia/genetics*
  • Cilia/pathology
  • Ciliopathies/genetics
  • Ciliopathies/pathology
  • DNA Helicases/genetics*
  • Humans
  • Minichromosome Maintenance Complex Component 2/genetics*
  • Minichromosome Maintenance Complex Component 7/genetics*
  • Mitosis/genetics
  • Transcription Initiation Site
  • Transcription, Genetic*
  • Zebrafish/genetics
PubMed
30329080 Full text @ Nucleic Acids Res.
Abstract
Minichromosome maintenance (MCM) proteins facilitate replication by licensing origins and unwinding the DNA double strand. Interestingly, the number of MCM hexamers greatly exceeds the number of firing origins suggesting additional roles of MCMs. Here we show a hitherto unanticipated function of MCM2 in cilia formation in human cells and zebrafish that is uncoupled from replication. Zebrafish depleted of MCM2 develop ciliopathy-phenotypes including microcephaly and aberrant heart looping due to malformed cilia. In non-cycling human fibroblasts, loss of MCM2 promotes transcription of a subset of genes, which cause cilia shortening and centriole overduplication. Chromatin immunoprecipitation experiments show that MCM2 binds to transcription start sites of cilia inhibiting genes. We propose that such binding may block RNA polymerase II-mediated transcription. Depletion of a second MCM (MCM7), which functions in complex with MCM2 during its canonical functions, reveals an overlapping cilia-deficiency phenotype likely unconnected to replication, although MCM7 appears to regulate a distinct subset of genes and pathways. Our data suggests that MCM2 and 7 exert a role in ciliogenesis in post-mitotic tissues.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping