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Mol Cell. 2018 May 3;70(3):395-407.e4. doi: 10.1016/j.molcel.2018.03.032.

The BUB3-BUB1 Complex Promotes Telomere DNA Replication.

Author information

1
Key Laboratory of Gene Engineering of the Ministry of Education and State Key Laboratory of Oncology in South China, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.
2
Verna and Marrs Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
3
Department of Pharmacology, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA.
4
Key Laboratory of Gene Engineering of the Ministry of Education and State Key Laboratory of Oncology in South China, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China. Electronic address: mawenbin@mail.sysu.edu.cn.
5
Key Laboratory of Gene Engineering of the Ministry of Education and State Key Laboratory of Oncology in South China, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China; Verna and Marrs Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Electronic address: songyang@bcm.edu.

Abstract

Telomeres and telomere-binding proteins form complex secondary nucleoprotein structures that are critical for genome integrity but can present serious challenges during telomere DNA replication. It remains unclear how telomere replication stress is resolved during S phase. Here, we show that the BUB3-BUB1 complex, a component in spindle assembly checkpoint, binds to telomeres during S phase and promotes telomere DNA replication. Loss of the BUB3-BUB1 complex results in telomere replication defects, including fragile and shortened telomeres. We also demonstrate that the telomere-binding ability of BUB3 and kinase activity of BUB1 are indispensable to BUB3-BUB1 function at telomeres. TRF2 targets BUB1-BUB3 to telomeres, and BUB1 can directly phosphorylate TRF1 and promote TRF1 recruitment of BLM helicase to overcome replication stress. Our findings have uncovered previously unknown roles for the BUB3-BUB1 complex in S phase and shed light on how proteins from diverse pathways function coordinately to ensure proper telomere replication and maintenance.

KEYWORDS:

BLM; BUB 3; BUB1; DNA replication; TRF1; TRF2; telomere; telomere length

Comment in

PMID:
29727616
PMCID:
PMC5982595
DOI:
10.1016/j.molcel.2018.03.032
[Indexed for MEDLINE]
Free PMC Article

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