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APE1 recruits ATRIP to ssDNA in an RPA-dependent and -independent manner to promote the ATR DNA damage response.
| Content Provider | Europe PMC |
|---|---|
| Author | Lin, Yunfeng Li, Jia Zhao, Haichao McMahon, Anne McGhee, Kelly Yan, Shan |
| Editor | Shinohara, Akira Struhl, Kevin |
| Copyright Year | 2023 |
| Abstract | Cells have evolved the DNA damage response (DDR) pathways in response to DNA replication stress or DNA damage. In the ATR-Chk1 DDR pathway, it has been proposed that ATR is recruited to RPA-coated single-stranded DNA (ssDNA) by direct ATRIP-RPA interaction. However, it remains elusive how ATRIP is recruited to ssDNA in an RPA-independent manner. Here, we provide evidence that APE1 directly associates ssDNA to recruit ATRIP onto ssDNA in an RPA-independent fashion. The N-terminal motif within APE1 is required and sufficient for the APE1-ATRIP interaction in vitro and the distinct APE1-ATRIP interaction is required for ATRIP recruitment to ssDNA and the ATR-Chk1 DDR pathway activation in Xenopus egg extracts. In addition, APE1 directly associates with RPA70 and RPA32 via two distinct motifs. Taken together, our evidence suggests that APE1 recruits ATRIP onto ssDNA in an RPA-dependent and -independent manner in the ATR DDR pathway. |
| Journal | eLife |
| Volume Number | 12 |
| PubMed Central reference number | PMC10202453 |
| PubMed reference number | 37216274 |
| e-ISSN | 2050084X |
| DOI | 10.7554/elife.82324 |
| Language | English |
| Publisher | eLife Sciences Publications, Ltd |
| Publisher Date | 2023-05-22 |
| Access Restriction | Open |
| Rights License | This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. © 2023, Lin et al |
| Subject Keyword | ATR APE1 RPA ATRIP ssDNA DDR Xenopus |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Microbiology Neuroscience Medicine Biochemistry, Genetics and Molecular Biology |
