Interaction of RECQL4 with poly(ADP‐ribose) is critical for the DNA double‐strand break response in human cells
To overcome genotoxicity, cells have evolved powerful and effective mechanisms to detect and respond to DNA lesions. RecQ Like Helicase‐4 (RECQL4) plays a vital role in DNA damage responses. RECQL4 is recruited to DNA double‐strand break (DSB) sites in a poly(ADP‐ribosyl)ation (PARylation)‐dependent...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | FEBS Open Bio |
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| Online Access: | https://doi.org/10.1002/2211-5463.13917 |
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| _version_ | 1841556989667180544 |
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| author | Sunyoung Shin Dongmin Kim Hyemi Kim Won‐Ho Cho Gyungmin Kim Joon‐Kyu Lee |
| author_facet | Sunyoung Shin Dongmin Kim Hyemi Kim Won‐Ho Cho Gyungmin Kim Joon‐Kyu Lee |
| author_sort | Sunyoung Shin |
| collection | DOAJ |
| description | To overcome genotoxicity, cells have evolved powerful and effective mechanisms to detect and respond to DNA lesions. RecQ Like Helicase‐4 (RECQL4) plays a vital role in DNA damage responses. RECQL4 is recruited to DNA double‐strand break (DSB) sites in a poly(ADP‐ribosyl)ation (PARylation)‐dependent manner, but the mechanism and significance of this process remain unclear. Here, we showed that the domain of RECQL4 recruited to DSBs in a PARylation‐dependent manner directly interacts with poly(ADP‐ribose) (PAR) and contains a PAR‐binding motif (PBM). By replacing this PBM with a PBM of hnRNPA2 or its mutated form, we demonstrated that the PBM in RECQL4 is required for PARylation‐dependent recruitment and the roles of RECQL4 in the DSB response. These results suggest that the direct interaction of RECQL4 with PAR is critical for proper cellular response to DSBs and provide insights to understand PARylation‐dependent control of the DSB response and cancer therapeutics using PARylation inhibitors. |
| format | Article |
| id | doaj-art-11b79a8d5022404b8ee1e0548047f8d2 |
| institution | Kabale University |
| issn | 2211-5463 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj-art-11b79a8d5022404b8ee1e0548047f8d22025-01-07T02:27:34ZengWileyFEBS Open Bio2211-54632025-01-0115114015010.1002/2211-5463.13917Interaction of RECQL4 with poly(ADP‐ribose) is critical for the DNA double‐strand break response in human cellsSunyoung Shin0Dongmin Kim1Hyemi Kim2Won‐Ho Cho3Gyungmin Kim4Joon‐Kyu Lee5Department of Biology Education Seoul National University KoreaDepartment of Biology Education Seoul National University KoreaDepartment of Biology Education Seoul National University KoreaDepartment of Biology Education Seoul National University KoreaDepartment of Biology Education Seoul National University KoreaDepartment of Biology Education Seoul National University KoreaTo overcome genotoxicity, cells have evolved powerful and effective mechanisms to detect and respond to DNA lesions. RecQ Like Helicase‐4 (RECQL4) plays a vital role in DNA damage responses. RECQL4 is recruited to DNA double‐strand break (DSB) sites in a poly(ADP‐ribosyl)ation (PARylation)‐dependent manner, but the mechanism and significance of this process remain unclear. Here, we showed that the domain of RECQL4 recruited to DSBs in a PARylation‐dependent manner directly interacts with poly(ADP‐ribose) (PAR) and contains a PAR‐binding motif (PBM). By replacing this PBM with a PBM of hnRNPA2 or its mutated form, we demonstrated that the PBM in RECQL4 is required for PARylation‐dependent recruitment and the roles of RECQL4 in the DSB response. These results suggest that the direct interaction of RECQL4 with PAR is critical for proper cellular response to DSBs and provide insights to understand PARylation‐dependent control of the DSB response and cancer therapeutics using PARylation inhibitors.https://doi.org/10.1002/2211-5463.13917DNA double‐strand breaksDNA repairpoly(ADP‐ribose) binding motifpoly(ADP‐ribosyl)ationRECQL4 |
| spellingShingle | Sunyoung Shin Dongmin Kim Hyemi Kim Won‐Ho Cho Gyungmin Kim Joon‐Kyu Lee Interaction of RECQL4 with poly(ADP‐ribose) is critical for the DNA double‐strand break response in human cells FEBS Open Bio DNA double‐strand breaks DNA repair poly(ADP‐ribose) binding motif poly(ADP‐ribosyl)ation RECQL4 |
| title | Interaction of RECQL4 with poly(ADP‐ribose) is critical for the DNA double‐strand break response in human cells |
| title_full | Interaction of RECQL4 with poly(ADP‐ribose) is critical for the DNA double‐strand break response in human cells |
| title_fullStr | Interaction of RECQL4 with poly(ADP‐ribose) is critical for the DNA double‐strand break response in human cells |
| title_full_unstemmed | Interaction of RECQL4 with poly(ADP‐ribose) is critical for the DNA double‐strand break response in human cells |
| title_short | Interaction of RECQL4 with poly(ADP‐ribose) is critical for the DNA double‐strand break response in human cells |
| title_sort | interaction of recql4 with poly adp ribose is critical for the dna double strand break response in human cells |
| topic | DNA double‐strand breaks DNA repair poly(ADP‐ribose) binding motif poly(ADP‐ribosyl)ation RECQL4 |
| url | https://doi.org/10.1002/2211-5463.13917 |
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