Di- and tri-methylation of histone H3K36 play distinct roles in DNA double-strand break repair
Histone H3 Lys36 (H3K36) methylation and its associated modifiers are crucial for DNA double-strand break (DSB) repair, but the mechanism governing whether and how different H3K36 methylation forms impact repair pathways is unclear. Here, we unveil the distinct roles of H3K36 dimethylation (H3K36me2...
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| Veröffentlicht in: | Science China. Life sciences 2024-06, Vol.67 (6), p.1089-1105 |
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| container_title | Science China. Life sciences |
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| creator | Chen, Runfa Zhao, Meng-Jie Li, Yu-Min Liu, Ao-Hui Wang, Ru-Xin Mei, Yu-Chao Chen, Xuefeng Du, Hai-Ning |
| description | Histone H3 Lys36 (H3K36) methylation and its associated modifiers are crucial for DNA double-strand break (DSB) repair, but the mechanism governing whether and how different H3K36 methylation forms impact repair pathways is unclear. Here, we unveil the distinct roles of H3K36 dimethylation (H3K36me2) and H3K36 trimethylation (H3K36me3) in DSB repair via non-homologous end joining (NHEJ) or homologous recombination (HR). Yeast cells lacking H3K36me2 or H3K36me3 exhibit reduced NHEJ or HR efficiency. yKu70 and Rfa1 bind H3K36me2- or H3K36me3-modified peptides and chromatin, respectively. Disrupting these interactions impairs yKu70 and Rfa1 recruitment to damaged H3K36me2- or H3K36me3-rich loci, increasing DNA damage sensitivity and decreasing repair efficiency. Conversely, H3K36me2-enriched intergenic regions and H3K36me3-enriched gene bodies independently recruit yKu70 or Rfa1 under DSB stress. Importantly, human KU70 and RPA1, the homologs of yKu70 and Rfa1, exclusively associate with H3K36me2 and H3K36me3 in a conserved manner. These findings provide valuable insights into how H3K36me2 and H3K36me3 regulate distinct DSB repair pathways, highlighting H3K36 methylation as a critical element in the choice of DSB repair pathway. |
| doi_str_mv | 10.1007/s11427-024-2543-9 |
| format | Article |
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Here, we unveil the distinct roles of H3K36 dimethylation (H3K36me2) and H3K36 trimethylation (H3K36me3) in DSB repair via non-homologous end joining (NHEJ) or homologous recombination (HR). Yeast cells lacking H3K36me2 or H3K36me3 exhibit reduced NHEJ or HR efficiency. yKu70 and Rfa1 bind H3K36me2- or H3K36me3-modified peptides and chromatin, respectively. Disrupting these interactions impairs yKu70 and Rfa1 recruitment to damaged H3K36me2- or H3K36me3-rich loci, increasing DNA damage sensitivity and decreasing repair efficiency. Conversely, H3K36me2-enriched intergenic regions and H3K36me3-enriched gene bodies independently recruit yKu70 or Rfa1 under DSB stress. Importantly, human KU70 and RPA1, the homologs of yKu70 and Rfa1, exclusively associate with H3K36me2 and H3K36me3 in a conserved manner. These findings provide valuable insights into how H3K36me2 and H3K36me3 regulate distinct DSB repair pathways, highlighting H3K36 methylation as a critical element in the choice of DSB repair pathway.</description><identifier>ISSN: 1674-7305</identifier><identifier>EISSN: 1869-1889</identifier><identifier>DOI: 10.1007/s11427-024-2543-9</identifier><identifier>PMID: 38842635</identifier><language>eng</language><publisher>Beijing: Science China Press</publisher><subject>Biomedical and Life Sciences ; Chromatin ; Chromatin - genetics ; Chromatin - metabolism ; Cover Article ; DNA Breaks, Double-Stranded ; DNA damage ; DNA End-Joining Repair ; DNA methylation ; DNA Repair ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Double-strand break repair ; Histone H3 ; Histones ; Histones - metabolism ; Homologous Recombination ; Humans ; Ku Autoantigen - genetics ; Ku Autoantigen - metabolism ; Life Sciences ; Methylation ; Non-homologous end joining ; Replication Protein A - genetics ; Replication Protein A - metabolism ; Saccharomyces cerevisiae - genetics ; Saccharomyces cerevisiae - metabolism ; Saccharomyces cerevisiae Proteins - genetics ; Saccharomyces cerevisiae Proteins - metabolism ; Yeast</subject><ispartof>Science China. Life sciences, 2024-06, Vol.67 (6), p.1089-1105</ispartof><rights>Science China Press 2024</rights><rights>2024. Science China Press.</rights><rights>Science China Press 2024.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c324t-cb9b67687c5759ce2067d89eb05f65c05eceaca3555bbb6d0a1366094a81251d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11427-024-2543-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11427-024-2543-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38842635$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Runfa</creatorcontrib><creatorcontrib>Zhao, Meng-Jie</creatorcontrib><creatorcontrib>Li, Yu-Min</creatorcontrib><creatorcontrib>Liu, Ao-Hui</creatorcontrib><creatorcontrib>Wang, Ru-Xin</creatorcontrib><creatorcontrib>Mei, Yu-Chao</creatorcontrib><creatorcontrib>Chen, Xuefeng</creatorcontrib><creatorcontrib>Du, Hai-Ning</creatorcontrib><title>Di- and tri-methylation of histone H3K36 play distinct roles in DNA double-strand break repair</title><title>Science China. Life sciences</title><addtitle>Sci. China Life Sci</addtitle><addtitle>Sci China Life Sci</addtitle><description>Histone H3 Lys36 (H3K36) methylation and its associated modifiers are crucial for DNA double-strand break (DSB) repair, but the mechanism governing whether and how different H3K36 methylation forms impact repair pathways is unclear. Here, we unveil the distinct roles of H3K36 dimethylation (H3K36me2) and H3K36 trimethylation (H3K36me3) in DSB repair via non-homologous end joining (NHEJ) or homologous recombination (HR). Yeast cells lacking H3K36me2 or H3K36me3 exhibit reduced NHEJ or HR efficiency. yKu70 and Rfa1 bind H3K36me2- or H3K36me3-modified peptides and chromatin, respectively. Disrupting these interactions impairs yKu70 and Rfa1 recruitment to damaged H3K36me2- or H3K36me3-rich loci, increasing DNA damage sensitivity and decreasing repair efficiency. Conversely, H3K36me2-enriched intergenic regions and H3K36me3-enriched gene bodies independently recruit yKu70 or Rfa1 under DSB stress. Importantly, human KU70 and RPA1, the homologs of yKu70 and Rfa1, exclusively associate with H3K36me2 and H3K36me3 in a conserved manner. These findings provide valuable insights into how H3K36me2 and H3K36me3 regulate distinct DSB repair pathways, highlighting H3K36 methylation as a critical element in the choice of DSB repair pathway.</description><subject>Biomedical and Life Sciences</subject><subject>Chromatin</subject><subject>Chromatin - genetics</subject><subject>Chromatin - metabolism</subject><subject>Cover Article</subject><subject>DNA Breaks, Double-Stranded</subject><subject>DNA damage</subject><subject>DNA End-Joining Repair</subject><subject>DNA methylation</subject><subject>DNA Repair</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Double-strand break repair</subject><subject>Histone H3</subject><subject>Histones</subject><subject>Histones - metabolism</subject><subject>Homologous Recombination</subject><subject>Humans</subject><subject>Ku Autoantigen - genetics</subject><subject>Ku Autoantigen - metabolism</subject><subject>Life Sciences</subject><subject>Methylation</subject><subject>Non-homologous end joining</subject><subject>Replication Protein A - genetics</subject><subject>Replication Protein A - metabolism</subject><subject>Saccharomyces cerevisiae - genetics</subject><subject>Saccharomyces cerevisiae - metabolism</subject><subject>Saccharomyces cerevisiae Proteins - genetics</subject><subject>Saccharomyces cerevisiae Proteins - metabolism</subject><subject>Yeast</subject><issn>1674-7305</issn><issn>1869-1889</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kD1PHDEQhi1EBOjCD6BBltLQOPHH-qtEQEIUBA1pY9neOTDsrS_2bnH_Pr4cECkSbsbyPPOO9SB0wuhnRqn-UhnruCaUd4TLThC7h46YUZYwY-x-uyvdES2oPETHtT7RdoSgXOsDdCiM6bgS8gj9ukwE-7HHU0lkBdPjZvBTyiPOS_yY6pRHwNfih1B4PfgN7ttTGuOESx6g4jTiy9tz3Oc5DEDqVLZJoYB_xgXWPpWP6MPSDxWOX-oC_fx6dX9xTW7uvn2_OL8hUfBuIjHYoLQyOkotbQROle6NhUDlUslIJUTw0QspZQhB9dQzoRS1nTeMS9aLBTrb5a5L_j1Dndwq1QjD4EfIc3WCKsk105Y19NN_6FOey9h-95cSQhqhGsV2VCy51gJLty5p5cvGMeq2_t3Ov2v-3da_s23m9CV5Divo3yZebTeA74DaWuMDlH-r30_9A4-ijdI</recordid><startdate>20240601</startdate><enddate>20240601</enddate><creator>Chen, Runfa</creator><creator>Zhao, Meng-Jie</creator><creator>Li, Yu-Min</creator><creator>Liu, Ao-Hui</creator><creator>Wang, Ru-Xin</creator><creator>Mei, Yu-Chao</creator><creator>Chen, Xuefeng</creator><creator>Du, Hai-Ning</creator><general>Science China Press</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TK</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>20240601</creationdate><title>Di- and tri-methylation of histone H3K36 play distinct roles in DNA double-strand break repair</title><author>Chen, Runfa ; 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Life sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Runfa</au><au>Zhao, Meng-Jie</au><au>Li, Yu-Min</au><au>Liu, Ao-Hui</au><au>Wang, Ru-Xin</au><au>Mei, Yu-Chao</au><au>Chen, Xuefeng</au><au>Du, Hai-Ning</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Di- and tri-methylation of histone H3K36 play distinct roles in DNA double-strand break repair</atitle><jtitle>Science China. Life sciences</jtitle><stitle>Sci. China Life Sci</stitle><addtitle>Sci China Life Sci</addtitle><date>2024-06-01</date><risdate>2024</risdate><volume>67</volume><issue>6</issue><spage>1089</spage><epage>1105</epage><pages>1089-1105</pages><issn>1674-7305</issn><eissn>1869-1889</eissn><abstract>Histone H3 Lys36 (H3K36) methylation and its associated modifiers are crucial for DNA double-strand break (DSB) repair, but the mechanism governing whether and how different H3K36 methylation forms impact repair pathways is unclear. Here, we unveil the distinct roles of H3K36 dimethylation (H3K36me2) and H3K36 trimethylation (H3K36me3) in DSB repair via non-homologous end joining (NHEJ) or homologous recombination (HR). Yeast cells lacking H3K36me2 or H3K36me3 exhibit reduced NHEJ or HR efficiency. yKu70 and Rfa1 bind H3K36me2- or H3K36me3-modified peptides and chromatin, respectively. Disrupting these interactions impairs yKu70 and Rfa1 recruitment to damaged H3K36me2- or H3K36me3-rich loci, increasing DNA damage sensitivity and decreasing repair efficiency. Conversely, H3K36me2-enriched intergenic regions and H3K36me3-enriched gene bodies independently recruit yKu70 or Rfa1 under DSB stress. Importantly, human KU70 and RPA1, the homologs of yKu70 and Rfa1, exclusively associate with H3K36me2 and H3K36me3 in a conserved manner. These findings provide valuable insights into how H3K36me2 and H3K36me3 regulate distinct DSB repair pathways, highlighting H3K36 methylation as a critical element in the choice of DSB repair pathway.</abstract><cop>Beijing</cop><pub>Science China Press</pub><pmid>38842635</pmid><doi>10.1007/s11427-024-2543-9</doi><tpages>17</tpages></addata></record> |
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| subjects | Biomedical and Life Sciences Chromatin Chromatin - genetics Chromatin - metabolism Cover Article DNA Breaks, Double-Stranded DNA damage DNA End-Joining Repair DNA methylation DNA Repair DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Double-strand break repair Histone H3 Histones Histones - metabolism Homologous Recombination Humans Ku Autoantigen - genetics Ku Autoantigen - metabolism Life Sciences Methylation Non-homologous end joining Replication Protein A - genetics Replication Protein A - metabolism Saccharomyces cerevisiae - genetics Saccharomyces cerevisiae - metabolism Saccharomyces cerevisiae Proteins - genetics Saccharomyces cerevisiae Proteins - metabolism Yeast |
| title | Di- and tri-methylation of histone H3K36 play distinct roles in DNA double-strand break repair |
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