APE1 recruits ATRIP to ssDNA in an RPA-dependent and -independent manner to promote the ATR DNA damage response
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 r...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-05-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/82324 |
| _version_ | 1797822248371879936 |
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| author | Yunfeng Lin Jia Li Haichao Zhao Anne McMahon Kelly McGhee Shan Yan |
| author_facet | Yunfeng Lin Jia Li Haichao Zhao Anne McMahon Kelly McGhee Shan Yan |
| author_sort | Yunfeng Lin |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T10:05:13Z |
| format | Article |
| id | doaj.art-3d346f98444e4520bce37da3067b3467 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-13T10:05:13Z |
| publishDate | 2023-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-3d346f98444e4520bce37da3067b34672023-05-22T15:57:28ZengeLife Sciences Publications LtdeLife2050-084X2023-05-011210.7554/eLife.82324APE1 recruits ATRIP to ssDNA in an RPA-dependent and -independent manner to promote the ATR DNA damage responseYunfeng Lin0Jia Li1Haichao Zhao2Anne McMahon3Kelly McGhee4Shan Yan5https://orcid.org/0000-0001-8106-6295Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, United StatesDepartment of Biological Sciences, University of North Carolina at Charlotte, Charlotte, United StatesDepartment of Biological Sciences, University of North Carolina at Charlotte, Charlotte, United StatesDepartment of Biological Sciences, University of North Carolina at Charlotte, Charlotte, United StatesDepartment of Biological Sciences, University of North Carolina at Charlotte, Charlotte, United StatesDepartment of Biological Sciences, University of North Carolina at Charlotte, Charlotte, United States; School of Data Science, University of North Carolina at Charlotte, Charlotte, United States; Center for Biomedical Engineering and Science, University of North Carolina at Charlotte, Charlotte, United StatesCells 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.https://elifesciences.org/articles/82324ATRAPE1RPAATRIPssDNADDR |
| spellingShingle | Yunfeng Lin Jia Li Haichao Zhao Anne McMahon Kelly McGhee Shan Yan APE1 recruits ATRIP to ssDNA in an RPA-dependent and -independent manner to promote the ATR DNA damage response eLife ATR APE1 RPA ATRIP ssDNA DDR |
| title | APE1 recruits ATRIP to ssDNA in an RPA-dependent and -independent manner to promote the ATR DNA damage response |
| title_full | APE1 recruits ATRIP to ssDNA in an RPA-dependent and -independent manner to promote the ATR DNA damage response |
| title_fullStr | APE1 recruits ATRIP to ssDNA in an RPA-dependent and -independent manner to promote the ATR DNA damage response |
| title_full_unstemmed | APE1 recruits ATRIP to ssDNA in an RPA-dependent and -independent manner to promote the ATR DNA damage response |
| title_short | APE1 recruits ATRIP to ssDNA in an RPA-dependent and -independent manner to promote the ATR DNA damage response |
| title_sort | ape1 recruits atrip to ssdna in an rpa dependent and independent manner to promote the atr dna damage response |
| topic | ATR APE1 RPA ATRIP ssDNA DDR |
| url | https://elifesciences.org/articles/82324 |
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