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Phosphorylation regulates human polη stability and damage bypass throughout the cell cycle
Federica Bertoletti1, Valentina Cea1, Chih-Chao Liang2
1Istituto di Genetica Molecolare-CNR, 27100, Pavia, Italy.
Nucleic Acids Research
|September 22, 2017
Summary
DNA translesion synthesis (TLS) polymerases are regulated by phosphorylation. New findings show cell cycle-dependent phosphorylation of polη enhances DNA repair and cell survival after UV damage.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- DNA translesion synthesis (TLS) is essential for replicating DNA with damage.
- TLS polymerases bypass DNA lesions but require tight regulation.
- Previous work identified polη phosphorylation at Serine 601 for damage bypass.
Purpose of the Study:
- Investigate cell cycle-dependent regulation of polη.
- Identify new phosphorylation sites and their functional significance.
- Understand how polη modulation impacts DNA repair and cell survival.
Main Methods:
- Phosphorylation site identification using kinase assays.
- Cell cycle analysis and Western blotting.
- UV irradiation survival assays.
Main Results:
- CDK2 phosphorylates polη at Serine 687 in a cell cycle-dependent manner.
- Serine 687 phosphorylation regulates polη stability, increasing its levels in late S and G2 phases.
- Phosphorylation of Serine 687, along with Serine 601 and others (S510, S512, S514), is crucial for UV damage bypass and cell survival.
Conclusions:
- Polη is regulated by distinct phosphorylation events during the cell cycle and in response to DNA damage.
- Cell cycle-dependent phosphorylation of polη at Serine 687 optimizes its function during critical replication and repair windows.
- Multiple polη phosphorylation sites collectively ensure efficient DNA repair and enhance cell survival following UV exposure.