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A DNA replication-independent function of pre-replication complex genes during cell invasion in C. elegans
Evelyn Lattmann1, Ting Deng1,2, Michael Walser1
1Department of Molecular Life Sciences, University of Zürich, Zürich, Switzerland.
Plos Biology
|February 22, 2022
Summary
The DNA pre-replication complex (pre-RC) regulates cell invasion, a key step in tumor metastasis and development. This complex acts as a transcriptional regulator in non-dividing cells to promote invasion.
Area of Science:
- Cell biology
- Developmental biology
- Cancer research
Background:
- Cell invasion is critical for tumor metastasis and embryonic development.
- The DNA pre-replication complex (pre-RC) is essential for DNA replication initiation.
Purpose of the Study:
- To identify novel regulators of cell invasion.
- To investigate the role of the DNA pre-replication complex (pre-RC) in cell invasion.
Main Methods:
- Screening of C. elegans orthologs of genes overexpressed in invasive melanoma cells.
- Investigating the function of pre-RC genes in anchor cell (AC) invasion.
- Analyzing the role of helicase activity and DNA replication initiation factors.
- Examining the regulation of extracellular matrix genes and PI3K signaling pathway.
Main Results:
- Components of the DNA pre-RC were identified as positive regulators of AC invasion.
- pre-RC genes function cell-autonomously in G1-arrested ACs, independent of DNA replication licensing.
- Helicase activity of the pre-RC is necessary, but downstream replication factors are not required for invasion.
- The pre-RC regulates extracellular matrix genes and PI3K signaling, with PI3K pathway activity partially rescuing invasion defects.
Conclusions:
- The DNA pre-RC, or a part of it, acts as a transcriptional regulator in postmitotic cells.
- The pre-RC facilitates the switch to an invasive phenotype by modulating gene expression and signaling pathways.
- This finding reveals a novel role for the pre-RC beyond DNA replication licensing.
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