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Mcl1p is a polymerase alpha replication accessory factor important for S-phase DNA damage survival
Dewight R Williams1, J R McIntosh
1Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado, USA. Dewight.williams@vanderbilt.edu
Eukaryotic Cell
|January 12, 2005
Summary
Mcl1p is a key fission yeast protein that binds DNA polymerase alpha during replication stress. Its dynamic interaction with Pol1p is crucial for the replication stress response.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Mcl1p is an essential fission yeast chromatin-binding protein involved in sister chromatid cohesion.
- Its essential function is thought to stem from its role as a Pol1p (DNA polymerase alpha) accessory protein, similar to Ctf4p.
Purpose of the Study:
- To investigate the interaction of Mcl1p with Pol1p.
- To determine Mcl1p's role in the DNA replication stress response in fission yeast.
Main Methods:
- Yeast genetics and molecular biology techniques.
- Characterization of an inducible mcl1+ allele.
- Analysis of protein interactions with Pol1p under replication stress conditions.
Main Results:
- Mcl1p binds Pol1p with high affinity during S phase and DNA damage.
- Altered Mcl1p expression causes sensitivity to DNA-damaging agents and synthetic lethality with replication checkpoint mutations.
- Mcl1p's interaction with chromatin and Pol1p is disrupted by S-phase checkpoint kinase manipulation during replication arrest.
Conclusions:
- Mcl1p is a dynamic component of the DNA polymerase alpha complex during replication.
- Mcl1p plays a critical role in the replication stress response pathway in fission yeast.