ArticleGenome biology2022
LAP2α preserves genome integrity through assisting RPA deposition on damaged chromatin.
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Article in Genome biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- LAP2α drives breast tumorigenesis by mitigating replication stress.Cell death & disease · 2026Article
- LAP2 Isoform Profile in Heart Ageing and in Cardiac Cell Proliferation and Differentiation: Input From CRISPR-Cas9-mediated LAP2a Knockdown in H9C2.International journal of medical sciences · 2026Article
- Nucleoplasmic Lamin A/C controls replication fork restart upon stress by modulating local H3K9me3 and ADP-ribosylation levels.Nature communications · 2025Article
- LAP2α orchestrates alternative lengthening of telomeres suppression through telomeric heterochromatin regulation with HDAC1: unveiling a potential therapeutic target.Cell death & disease · 2024Article
- The expression and role of the Lem-D proteins Ankle2, Emerin, Lemd2, and TMPO in triple-negative breast cancer cell growth.Frontiers in oncology · 2024Article
- DNA replication and replication stress response in the context of nuclear architecture.Chromosoma · 2024Review
- SIRT7 Downregulation Promotes Breast Cancer Metastasis Via LAP2α-Induced Chromosomal Instability.International journal of biological sciences · 2023Article
- LAP2α preserves genome integrity through assisting RPA deposition on damaged chromatin.Genome biology · 2022Article
- Innate immunity mediator STING modulates nascent DNA metabolism at stalled forks in human cells.Frontiers in molecular biosciences · 2022Article
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Authors and funding
15 authors at 3 institutions in 2 countries.
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, Tianjin, 300070, China.
Qi Zhang *Department of Clinical Laboratory, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
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, Tianjin, 300070, China.
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, Tianjin, 300070, China.
Qiushi GuoState 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, Tianjin, 300070, China.
Ling LiuState 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, Tianjin, 300070, China.
Shanshan TianState 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, Tianjin, 300070, China.
Jihui HaoState 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, Tianjin, 300070, China.
Yi ZhuState 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, Tianjin, 300070, China.
Kai ZhangState 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, Tianjin, 300070, China.
Ding AiState 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, Tianjin, 300070, China.
Jie YangState 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, Tianjin, 300070, China.
Zhi YaoState 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, Tianjin, 300070, China.
Roland FoisnerMax Perutz Laboratories, Center of Medical Biochemistry, Medical University of Vienna, Vienna Biocenter (VBC), Vienna, Austria.
Lei ShiState 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, Tianjin, 300070, China. shilei@tmu.edu.cn.ORCID 0000-0003-1679-3618
Tianjin Medical University General Hospital · CNFirst Affiliated Hospital of Xi'an Jiaotong University · CNMax Perutz Labs · AT
Funding
Austrian Science Fund FWF W 1261
Abstract
backgroundSingle-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.
resultsHere, 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.
conclusionsOur study provides mechanistic insight into RPA deposition in response to DNA damage and reveals a genome protection role of LAP2α.
Indexed as
ChromatinReplication Protein ADNA-Binding ProteinsDNA DamageDNA RepairDNA ReplicationDNA, Single-StrandedMembrane ProteinsChromatinDNA-Binding ProteinsDNA, Single-Strandedlamina-associated polypeptide 2Membrane ProteinsReplication Protein AATR activationGenome stabilityHomologous recombinationLAP2αPARP1RPA loading
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.