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G2-seq: A High Throughput Sequencing-based Technique for Identifying Late Replicating Regions of the Genome
Published on: March 22, 2018
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The TRESLIN-MTBP complex couples completion of DNA replication with S/G2 transition
Gijs Zonderland1, Riccardo Vanzo1, Sampath Amitash Gadi1
1Center for Chromosome Stability, Institute for Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
Molecular Cell
|September 1, 2022
Summary
The TRESLIN-MTBP complex ensures DNA replication completion before the S/G2 transition, acting independently of ATR/CHK1 kinases. This complex monitors replication forks and origin firing rates for proper cell-cycle control.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- The S/G2 cell-cycle transition is crucial for genomic stability.
- ATR/CHK1 kinases are canonical regulators of DNA replication checkpoints.
- The precise mechanisms ensuring replication completion before G2 entry are not fully elucidated.
Purpose of the Study:
- To investigate the role of the TRESLIN-MTBP complex in regulating the S/G2 transition.
- To determine if TRESLIN-MTBP acts independently of the ATR/CHK1 pathway.
- To elucidate the molecular mechanism by which TRESLIN-MTBP monitors DNA replication.
Main Methods:
- Biochemical assays to study protein complex formation and release.
- Cell-based assays to monitor cell-cycle progression.
- Analysis of origin firing and replication fork activation.
Main Results:
- The TRESLIN-MTBP complex prevents premature G2 entry from early S-phase.
- TRESLIN-MTBP functions independently of ATR/CHK1 kinases.
- TRESLIN-MTBP is transiently recruited to pre-replication complexes and released upon CDC45 recruitment.
- This complex acts as a surveillance system monitoring replication fork activation and origin firing rate.
Conclusions:
- TRESLIN-MTBP acts as a novel, independent regulator of the S/G2 transition.
- This complex ensures DNA replication completion by sensing the rate of origin firing.
- TRESLIN-MTBP represents a key player in cell-cycle control beyond canonical checkpoints.
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