Genome Biology (Feb 2022)
LAP2α preserves genome integrity through assisting RPA deposition on damaged chromatin
- Kaiwen Bao,
- Qi Zhang,
- Shuai Liu,
- Nan Song,
- Qiushi Guo,
- Ling Liu,
- Shanshan Tian,
- Jihui Hao,
- Yi Zhu,
- Kai Zhang,
- Ding Ai,
- Jie Yang,
- Zhi Yao,
- Roland Foisner,
- Lei Shi
Affiliations
- Kaiwen Bao
- State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University General Hospital, School of Basic Medical Sciences, Tianjin Medical University
- Qi Zhang
- Department of Clinical Laboratory, First Affiliated Hospital of Xi’an Jiaotong University
- Shuai Liu
- State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University General Hospital, School of Basic Medical Sciences, Tianjin Medical University
- Nan Song
- State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University General Hospital, School of Basic Medical Sciences, Tianjin Medical University
- Qiushi Guo
- State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University General Hospital, School of Basic Medical Sciences, Tianjin Medical University
- Ling Liu
- State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University General Hospital, School of Basic Medical Sciences, Tianjin Medical University
- Shanshan Tian
- State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University General Hospital, School of Basic Medical Sciences, Tianjin Medical University
- Jihui Hao
- State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University General Hospital, School of Basic Medical Sciences, Tianjin Medical University
- Yi Zhu
- State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University General Hospital, School of Basic Medical Sciences, Tianjin Medical University
- Kai Zhang
- State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University General Hospital, School of Basic Medical Sciences, Tianjin Medical University
- Ding Ai
- State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University General Hospital, School of Basic Medical Sciences, Tianjin Medical University
- Jie Yang
- State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University General Hospital, School of Basic Medical Sciences, Tianjin Medical University
- Zhi Yao
- State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University General Hospital, School of Basic Medical Sciences, Tianjin Medical University
- Roland Foisner
- Max Perutz Laboratories, Center of Medical Biochemistry, Medical University of Vienna, Vienna Biocenter (VBC)
- Lei Shi
- State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University General Hospital, School of Basic Medical Sciences, Tianjin Medical University
- DOI
- https://doi.org/10.1186/s13059-022-02638-6
- Journal volume & issue
-
Vol. 23,
no. 1
pp. 1 – 22
Abstract
Abstract Background Single-stranded DNA (ssDNA) coated with replication protein A (RPA) acts as a key platform for the recruitment and exchange of genome maintenance factors in DNA damage response. Yet, how the formation of the ssDNA-RPA intermediate is regulated remains elusive. Results Here, we report that the lamin-associated protein LAP2α is physically associated with RPA, and LAP2α preferentially facilitates RPA deposition on damaged chromatin via physical contacts between LAP2α and RPA1. Importantly, LAP2α-promoted RPA binding to ssDNA plays a critical role in protection of replication forks, activation of ATR, and repair of damaged DNA. We further demonstrate that the preference of LAP2α-promoted RPA loading on damaged chromatin depends on poly ADP-ribose polymerase PARP1, but not poly(ADP-ribosyl)ation. Conclusions Our study provides mechanistic insight into RPA deposition in response to DNA damage and reveals a genome protection role of LAP2α.
Keywords