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| Rad6-Bre1-mediated H2B ubiquitination regulates telomere replication by promoting telomere-end resection | |
| 2017-04-07 | |
| Source Publication | NUCLEIC ACIDS RESEARCH
 |
| ISSN | 0305-1048 |
| Volume | 45Issue:6Pages:3308-3322 |
| Status | 已发表 |
| DOI | 10.1093/nar/gkx101 |
| Abstract | Rad6 and Bre1, ubiquitin-conjugating E2 and E3 enzymes respectively, are responsible for histone H2B lysine 123 mono-ubiquitination (H2Bub1) in Saccha-romyces cerevisiae. Previous studies have shown that Rad6 and Bre1 regulate telomere length and recombination. However, the underlying molecular mechanism remains largely unknown. Here we report that H2BK123 mutation results in telomere shortening, while inactivation of Ubp8 and/or Ubp10, deubiquitinases of H2Bub1, leads to telomere lengthening in Rad6-Bre1-dependent manner. In telomerase-deficient cells, inactivation of Rad6-Bre1 pathway retards telomere shortening rate and the onset of senescence, while deletion of UBP8 and/or UBP10 accelerates senescence. Thus, Rad6-Bre1 pathway regulates both telomere length and recombination through its role in H2Bub1. Additionally, inactivation of both Rad6-Bre1-H2Bub1 and Mre11-Rad50Xrs2 (MRX) pathways causes synthetic growth defects and telomere shortening in telomeraseproficient cells, and significantly accelerates senescence and eliminates type II telomere recombination in telomerase-deficient cells. Furthermore, RAD6 or BRE1 deletion, or H2BK123Rmutation decreases the accumulation of ssDNA at telomere ends. These results support the model that Rad6-Bre1-H2Bub1 cooperates with MRX to promote telomere-end resection and thus positively regulates both telomeraseand recombination-dependent telomere replication. This study provides a mechanistic link between histone H2B ubiquitination and telomere replication. |
| Indexed By | SCI |
| Language | 英语 |
| Funding Project | NSFC[31500658] |
| WOS Research Area | Biochemistry & Molecular Biology |
| WOS Subject | Biochemistry & Molecular Biology |
| WOS ID | WOS:000398376200039 |
| Publisher | OXFORD UNIV PRESS |
| WOS Keyword | DOUBLE-STRAND BREAKS ; DE-NOVO TELOMERE ; SACCHAROMYCES-CEREVISIAE ; HISTONE H2B ; YEAST TELOMERES ; BUDDING YEAST ; DNA ; MAINTENANCE ; RECOMBINATION ; SENESCENCE |
| Original Document Type | Article |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1419 |
| Collection | 生命科学与技术学院_特聘教授组_周金秋组 |
| Corresponding Author | Zhou, Jin-Qiu |
| Affiliation | 1.Chinese Acad Sci, Univ Chinese Acad Sci, Ctr Excellence Mol Cell Sci,State Key Lab Mol Bio, Innovat Ctr Cell Signaling Network,Shanghai Inst, 320 Yueyang Rd, Shanghai 200031, Peoples R China 2.Shanghai Tech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China |
| Corresponding Author Affilication | School of Life Science and Technology |
| Recommended Citation GB/T 7714 | Wu, Zhenfang,Liu, Jun,Zhang, Qiong-Di,et al. Rad6-Bre1-mediated H2B ubiquitination regulates telomere replication by promoting telomere-end resection[J]. NUCLEIC ACIDS RESEARCH,2017,45(6):3308-3322. |
| APA | Wu, Zhenfang,Liu, Jun,Zhang, Qiong-Di,Lv, De-Kang,Wu, Nian-Feng,&Zhou, Jin-Qiu.(2017).Rad6-Bre1-mediated H2B ubiquitination regulates telomere replication by promoting telomere-end resection.NUCLEIC ACIDS RESEARCH,45(6),3308-3322. |
| MLA | Wu, Zhenfang,et al."Rad6-Bre1-mediated H2B ubiquitination regulates telomere replication by promoting telomere-end resection".NUCLEIC ACIDS RESEARCH 45.6(2017):3308-3322. |
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