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- Publisher Website: 10.1093/nar/gkz263
- Scopus: eid_2-s2.0-85069295031
- PMID: 30982887
- WOS: WOS:000475891900023
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Article: LC8/DYNLL1 is a 53BP1 effector and regulates checkpoint activation
Title | LC8/DYNLL1 is a 53BP1 effector and regulates checkpoint activation |
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Authors | |
Issue Date | 2019 |
Publisher | Oxford University Press: Policy C - Creative Commons Attribution and Creative Commons Attribution Non-Commercial. The Journal's web site is located at http://nar.oxfordjournals.org/ |
Citation | Nucleic Acids Research, 2019, v. 47 n. 12, p. 6236-6249 How to Cite? |
Abstract | The tumor suppressor protein 53BP1 plays key roles in response to DNA double-strand breaks (DSBs) by serving as a master scaffold at the damaged chromatin. Current evidence indicates that 53BP1 assembles a cohort of DNA damage response (DDR) factors to distinctly execute its repertoire of DSB responses, including checkpoint activation and non-homologous end joining (NHEJ) repair. Here, we have uncovered LC8 (a.k.a. DYNLL1) as an important 53BP1 effector. We found that LC8 accumulates at laser-induced DNA damage tracks in a 53BP1-dependent manner and requires the canonical H2AX-MDC1-RNF8-RNF168 signal transduction cascade. Accordingly, genetic inactivation of LC8 or its interaction with 53BP1 resulted in checkpoint defects. Importantly, loss of LC8 alleviated the hypersensitivity of BRCA1-depleted cells to ionizing radiation and PARP inhibition, highlighting the 53BP1-LC8 module in counteracting BRCA1-dependent functions in the DDR. Together, these data establish LC8 as an important mediator of a subset of 53BP1-dependent DSB responses. |
Persistent Identifier | http://hdl.handle.net/10722/293500 |
ISSN | 2023 Impact Factor: 16.6 2023 SCImago Journal Rankings: 7.048 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | West, KL | - |
dc.contributor.author | Kelliher, JL | - |
dc.contributor.author | Xu, Z | - |
dc.contributor.author | AN, L | - |
dc.contributor.author | Reed, MR | - |
dc.contributor.author | Eoff, RL | - |
dc.contributor.author | Wang, J | - |
dc.contributor.author | Huen, MSY | - |
dc.contributor.author | Leung, JWC | - |
dc.date.accessioned | 2020-11-23T08:17:40Z | - |
dc.date.available | 2020-11-23T08:17:40Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Nucleic Acids Research, 2019, v. 47 n. 12, p. 6236-6249 | - |
dc.identifier.issn | 0305-1048 | - |
dc.identifier.uri | http://hdl.handle.net/10722/293500 | - |
dc.description.abstract | The tumor suppressor protein 53BP1 plays key roles in response to DNA double-strand breaks (DSBs) by serving as a master scaffold at the damaged chromatin. Current evidence indicates that 53BP1 assembles a cohort of DNA damage response (DDR) factors to distinctly execute its repertoire of DSB responses, including checkpoint activation and non-homologous end joining (NHEJ) repair. Here, we have uncovered LC8 (a.k.a. DYNLL1) as an important 53BP1 effector. We found that LC8 accumulates at laser-induced DNA damage tracks in a 53BP1-dependent manner and requires the canonical H2AX-MDC1-RNF8-RNF168 signal transduction cascade. Accordingly, genetic inactivation of LC8 or its interaction with 53BP1 resulted in checkpoint defects. Importantly, loss of LC8 alleviated the hypersensitivity of BRCA1-depleted cells to ionizing radiation and PARP inhibition, highlighting the 53BP1-LC8 module in counteracting BRCA1-dependent functions in the DDR. Together, these data establish LC8 as an important mediator of a subset of 53BP1-dependent DSB responses. | - |
dc.language | eng | - |
dc.publisher | Oxford University Press: Policy C - Creative Commons Attribution and Creative Commons Attribution Non-Commercial. The Journal's web site is located at http://nar.oxfordjournals.org/ | - |
dc.relation.ispartof | Nucleic Acids Research | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.title | LC8/DYNLL1 is a 53BP1 effector and regulates checkpoint activation | - |
dc.type | Article | - |
dc.identifier.email | Huen, MSY: huen.michael@hku.hk | - |
dc.identifier.authority | Huen, MSY=rp01336 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1093/nar/gkz263 | - |
dc.identifier.pmid | 30982887 | - |
dc.identifier.pmcid | PMC6614850 | - |
dc.identifier.scopus | eid_2-s2.0-85069295031 | - |
dc.identifier.hkuros | 319477 | - |
dc.identifier.volume | 47 | - |
dc.identifier.issue | 12 | - |
dc.identifier.spage | 6236 | - |
dc.identifier.epage | 6249 | - |
dc.identifier.isi | WOS:000475891900023 | - |
dc.publisher.place | United Kingdom | - |