期刊
MOLECULAR CELL
卷 70, 期 3, 页码 395-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2018.03.032
关键词
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资金
- National Key Research and Development Program of China [2017YFA0102801]
- National Natural Science Foundation of China [91640119, 81330055, 91749113, 31570827]
- Science and Technology Planning Project of Guangdong Province [2015B020228002]
- Guangzhou Science and Technology Project [201605030012]
- NIH [HL131744, CA211653]
- Welch Foundation [Q-1673, I-1441]
- CPRIT [RP160462]
- C-BASS core
- Dan L. Duncan Cancer Center [P30CA125123]
- NATIONAL CANCER INSTITUTE [P30CA125123, R01CA211653] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL131744] Funding Source: NIH RePORTER
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.
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