Chk1 and Claspin potentiate PCNA ubiquitination
Copyright policy )Chk1 and Claspin potentiate PCNA ubiquitination
Chk1 is a kinase crucial for genomic integrity and an effector of ATR (ATM and Rad3-realated) in DNA damage response. Here, we show that Chk1 regulates the DNA damage-induced ubiquitination of proliferating cell nuclear antigen (PCNA), which facilitates the continuous replication of damaged DNA. Surprisingly, this Chk1 function requires the DNA replication protein Claspin but not ATR. Claspin, which is stabilized by Chk1, regulates the binding of the ubiquitin ligase Rad18 to chromatin. Timeless, a Claspin-associating protein, is also required for efficient PCNA ubiquitination. Thus, Chk1 and the Claspin–Timeless module of replication forks not only participate in ATR signaling, but also protect stressed forks independently of ATR.
- Harvard University United States
DNA Replication, Ultraviolet Rays, Morpholines, Blotting, Western, Ubiquitination, Cell Cycle Proteins, Ataxia Telangiectasia Mutated Proteins, Protein Serine-Threonine Kinases, Transfection, Pyrones, Cell Line, Tumor, Proliferating Cell Nuclear Antigen, Checkpoint Kinase 1, Humans, Hydroxyurea, RNA, Small Interfering, Protein Kinases, Adaptor Proteins, Signal Transducing, HeLa Cells, Plasmids
DNA Replication, Ultraviolet Rays, Morpholines, Blotting, Western, Ubiquitination, Cell Cycle Proteins, Ataxia Telangiectasia Mutated Proteins, Protein Serine-Threonine Kinases, Transfection, Pyrones, Cell Line, Tumor, Proliferating Cell Nuclear Antigen, Checkpoint Kinase 1, Humans, Hydroxyurea, RNA, Small Interfering, Protein Kinases, Adaptor Proteins, Signal Transducing, HeLa Cells, Plasmids
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