Homology directed telomere clustering, ultrabright telomere formation and nuclear envelope rupture in cells lacking TRF2(B) and RAP1

doi:10.1038/s41467-023-37761-w

	Homology directed telomere clustering, ultrabright telomere formation and nuclear envelope rupture in cells lacking TRF2(B) and RAP1
	Rai, Rekha 1; Biju, Kevin 1,2; Sun, Wenqi 3,4; Sodeinde, Tori 1; Al-Hiysat, Amer 1; Morgan, Jaida 1; Ye, Xianwen4,5 ; Li, Xueqing 3,4; Chen, Yong3,4,5 ; Chang, Sandy 1,6,7
	2023-04-14
发表期刊	NATURE COMMUNICATIONS (IF:14.7[JCR-2023],16.1[5-Year])
EISSN	2041-1723
卷号	14 期号:1
发表状态	已发表
DOI	10.1038/s41467-023-37761-w
摘要	["Double-strand breaks (DSBs) due to genotoxic stress represent potential threats to genome stability. Dysfunctional telomeres are recognized as DSBs and are repaired by distinct DNA repair mechanisms. RAP1 and TRF2 are telomere binding proteins essential to protect telomeres from engaging in homology directed repair (HDR), but how this occurs remains unclear. In this study, we examined how the basic domain of TRF2 (TRF2(B)) and RAP1 cooperate to repress HDR at telomeres. Telomeres lacking TRF2(B) and RAP1 cluster into structures termed ultrabright telomeres (UTs). HDR factors localize to UTs, and UT formation is abolished by RNaseH1, DDX21 and ADAR1p110, suggesting that they contain DNA-RNA hybrids. Interaction between the BRCT domain of RAP1 and KU70/KU80 is also required to repress UT formation. Expressing TRF2( increment B) in Rap1(-/-) cells resulted in aberrant lamin A localization in the nuclear envelope and dramatically increased UT formation. Expressing lamin A phosphomimetic mutants induced nuclear envelope rupturing and aberrant HDR-mediated UT formation. Our results highlight the importance of shelterin and proteins in the nuclear envelope in repressing aberrant telomere-telomere recombination to maintain telomere homeostasis.","The telomere binding proteins RAP1 and TRF2 protect telomeres from engaging in homology directed repair (HDR). In this study, the authors reveal that the basic domain of TRF2 (TRF2B) and RAP 1 cooperate to repress HDR at telomeres and prevent formation ultrabright telomere structures."]
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收录类别	SCI
语种	英语
资助项目	Strategic Priority Research Program of the Chinese Academy of Sciences[XDB37010303] ; Department of Defense["W81XWH191005","BC210086"] ; NIH["RO1CA202816","RO1GM141350"]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000969250300012
出版者	NATURE PORTFOLIO
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/305008
专题	生命科学与技术学院生命科学与技术学院_特聘教授组_陈勇组生命科学与技术学院_硕士生
通讯作者	Rai, Rekha; Chang, Sandy
作者单位	1.Yale Univ, Sch Med, Dept Lab Med, 330 Cedar St, New Haven, CT 06520 USA 2.Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA 3.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Natl Ctr Prot Sci Shanghai, State Key Lab Mol Biol,Ctr Excellence Mol Cell Sci, Shanghai 200031, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 5.ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China 6.Yale Univ, Sch Med, Dept Pathol, 330 Cedar St, New Haven, CT 06520 USA 7.Yale Univ, Sch Med, Dept Mol Biophys & Biochem, 330 Cedar St, New Haven, CT 06520 USA
推荐引用方式 GB/T 7714	Rai, Rekha,Biju, Kevin,Sun, Wenqi,et al. Homology directed telomere clustering, ultrabright telomere formation and nuclear envelope rupture in cells lacking TRF2(B) and RAP1[J]. NATURE COMMUNICATIONS,2023,14(1).
APA	Rai, Rekha.,Biju, Kevin.,Sun, Wenqi.,Sodeinde, Tori.,Al-Hiysat, Amer.,...&Chang, Sandy.(2023).Homology directed telomere clustering, ultrabright telomere formation and nuclear envelope rupture in cells lacking TRF2(B) and RAP1.NATURE COMMUNICATIONS,14(1).
MLA	Rai, Rekha,et al."Homology directed telomere clustering, ultrabright telomere formation and nuclear envelope rupture in cells lacking TRF2(B) and RAP1".NATURE COMMUNICATIONS 14.1(2023).