Dimerization of MORC2 through its C-terminal coiled-coil domain enhances chromatin dynamics and promotes DNA repair
Abstract Decondesation of the highly compacted chromatin architecture is essential for efficient DNA repair, but how this is achieved remains largely unknown. Here, we report that microrchidia family CW-type zinc finger protein 2 (MORC2), a newly identified ATPase-dependent chromatin remodeling enzy...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-12-01
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| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12964-019-0477-5 |
| _version_ | 1819173776284188672 |
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| author | Hong-Yan Xie Tai-Mei Zhang Shu-Yuan Hu Zhi-Ming Shao Da-Qiang Li |
| author_facet | Hong-Yan Xie Tai-Mei Zhang Shu-Yuan Hu Zhi-Ming Shao Da-Qiang Li |
| author_sort | Hong-Yan Xie |
| collection | DOAJ |
| description | Abstract Decondesation of the highly compacted chromatin architecture is essential for efficient DNA repair, but how this is achieved remains largely unknown. Here, we report that microrchidia family CW-type zinc finger protein 2 (MORC2), a newly identified ATPase-dependent chromatin remodeling enzyme, is required for nucleosome destabilization after DNA damage through loosening the histone-DNA interaction. Depletion of MORC2 attenuates phosphorylated histone H2AX (γH2AX) focal formation, compromises the recruitment of DNA repair proteins, BRCA1, 53BP1, and Rad51, to sites of DNA damage, and consequently reduces cell survival following treatment with DNA-damaging chemotherapeutic drug camptothecin (CPT). Furthermore, we demonstrate that MORC2 can form a homodimer through its C-terminal coiled-coil (CC) domain, a process that is enhanced in response to CPT-induced DNA damage. Deletion of the C-terminal CC domain in MORC2 disrupts its homodimer formation and impairs its ability to destabilize histone-DNA interaction after DNA damage. Consistently, expression of dimerization-defective MORC2 mutant results in impaired the recruitment of DNA repair proteins to damaged chromatin and decreased cell survival after CPT treatment. Together, these findings uncover a new mechanism for MORC2 in modulating chromatin dynamics and DDR signaling through its c-terminal dimerization. |
| first_indexed | 2024-12-22T20:28:27Z |
| format | Article |
| id | doaj.art-f8ec9b78838b4d2eaf467ce3b4b3b0cc |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-12-22T20:28:27Z |
| publishDate | 2019-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-f8ec9b78838b4d2eaf467ce3b4b3b0cc2022-12-21T18:13:40ZengBMCCell Communication and Signaling1478-811X2019-12-0117111110.1186/s12964-019-0477-5Dimerization of MORC2 through its C-terminal coiled-coil domain enhances chromatin dynamics and promotes DNA repairHong-Yan Xie0Tai-Mei Zhang1Shu-Yuan Hu2Zhi-Ming Shao3Da-Qiang Li4Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan UniversityShanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan UniversityShanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan UniversityShanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan UniversityShanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan UniversityAbstract Decondesation of the highly compacted chromatin architecture is essential for efficient DNA repair, but how this is achieved remains largely unknown. Here, we report that microrchidia family CW-type zinc finger protein 2 (MORC2), a newly identified ATPase-dependent chromatin remodeling enzyme, is required for nucleosome destabilization after DNA damage through loosening the histone-DNA interaction. Depletion of MORC2 attenuates phosphorylated histone H2AX (γH2AX) focal formation, compromises the recruitment of DNA repair proteins, BRCA1, 53BP1, and Rad51, to sites of DNA damage, and consequently reduces cell survival following treatment with DNA-damaging chemotherapeutic drug camptothecin (CPT). Furthermore, we demonstrate that MORC2 can form a homodimer through its C-terminal coiled-coil (CC) domain, a process that is enhanced in response to CPT-induced DNA damage. Deletion of the C-terminal CC domain in MORC2 disrupts its homodimer formation and impairs its ability to destabilize histone-DNA interaction after DNA damage. Consistently, expression of dimerization-defective MORC2 mutant results in impaired the recruitment of DNA repair proteins to damaged chromatin and decreased cell survival after CPT treatment. Together, these findings uncover a new mechanism for MORC2 in modulating chromatin dynamics and DDR signaling through its c-terminal dimerization.https://doi.org/10.1186/s12964-019-0477-5DNA damage responseChromatin remodelingMORC2Coiled-coil domainDimerization |
| spellingShingle | Hong-Yan Xie Tai-Mei Zhang Shu-Yuan Hu Zhi-Ming Shao Da-Qiang Li Dimerization of MORC2 through its C-terminal coiled-coil domain enhances chromatin dynamics and promotes DNA repair Cell Communication and Signaling DNA damage response Chromatin remodeling MORC2 Coiled-coil domain Dimerization |
| title | Dimerization of MORC2 through its C-terminal coiled-coil domain enhances chromatin dynamics and promotes DNA repair |
| title_full | Dimerization of MORC2 through its C-terminal coiled-coil domain enhances chromatin dynamics and promotes DNA repair |
| title_fullStr | Dimerization of MORC2 through its C-terminal coiled-coil domain enhances chromatin dynamics and promotes DNA repair |
| title_full_unstemmed | Dimerization of MORC2 through its C-terminal coiled-coil domain enhances chromatin dynamics and promotes DNA repair |
| title_short | Dimerization of MORC2 through its C-terminal coiled-coil domain enhances chromatin dynamics and promotes DNA repair |
| title_sort | dimerization of morc2 through its c terminal coiled coil domain enhances chromatin dynamics and promotes dna repair |
| topic | DNA damage response Chromatin remodeling MORC2 Coiled-coil domain Dimerization |
| url | https://doi.org/10.1186/s12964-019-0477-5 |
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