Rad6-Bre1-mediated H2B ubiquitination regulates telomere replication by promoting telomere-end resection

doi:10.1093/nar/gkx101

	Rad6-Bre1-mediated H2B ubiquitination regulates telomere replication by promoting telomere-end resection
	Wu, Zhenfang 1; Liu, Jun 1; Zhang, Qiong-Di 1; Lv, De-Kang 1; Wu, Nian-Feng 1; Zhou, Jin-Qiu1,2
	2017-04-07
发表期刊	NUCLEIC ACIDS RESEARCH
ISSN	0305-1048
卷号	45 期号:6 页码:3308-3322
发表状态	已发表
DOI	10.1093/nar/gkx101
摘要	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.
收录类别	SCI
语种	英语
资助项目	NSFC[31500658]
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:000398376200039
出版者	OXFORD UNIV PRESS
WOS关键词	DOUBLE-STRAND BREAKS ; DE-NOVO TELOMERE ; SACCHAROMYCES-CEREVISIAE ; HISTONE H2B ; YEAST TELOMERES ; BUDDING YEAST ; DNA ; MAINTENANCE ; RECOMBINATION ; SENESCENCE
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1419
专题	生命科学与技术学院_特聘教授组_周金秋组
通讯作者	Zhou, Jin-Qiu
作者单位	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
通讯作者单位	生命科学与技术学院
推荐引用方式 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.