@article{4049431150ca4a4c9d81a333b660141a,
title = "The BUB3-BUB1 Complex Promotes Telomere DNA Replication",
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. Telomeres and telomere-binding proteins form nucleoprotein structures that can present serious challenges during telomere DNA replication. Li et al. show that TRF2 targets the BUB1-BUB3 complex to telomeres during S phase and promotes telomere DNA replication. BUB1 phosphorylates TRF1 to promote recruitment of BLM helicase to overcome replication stress.",
keywords = "BLM, BUB 3, BUB1, DNA replication, TRF1, TRF2, telomere, telomere length",
author = "Feng Li and Hyeung Kim and Zhejian Ji and Tianpeng Zhang and Bohong Chen and Yuanlong Ge and Yang Hu and Xuyang Feng and Xin Han and Huimin Xu and Youwei Zhang and Hongtao Yu and Dan Liu and Wenbin Ma and Zhou Songyang",
note = "Funding Information: We thank Yuxi Chen and Junyan Feng for their assistance with protein expression and purification. We are also grateful to members of the Songyang laboratory for their insightful discussions and technical assistance. Our work was supported by grants from National Key Research and Development Program of China ( 2017YFA0102801 ), the National Natural Science Foundation of China ( 91640119 , 81330055 , 91749113 , and 31570827 ), Science and Technology Planning Project of Guangdong Province ( 2015B020228002 ), Guangzhou Science and Technology Project ( 201605030012 ), the NIH ( HL131744 and CA211653 ), the Welch Foundation ( Q-1673 and I-1441 ), and CPRIT RP160462 . H.Y. is an Investigator with the Howard Hughes Medical Institute. We would also like to acknowledge the support of the C-BASS core and the Dan L. Duncan Cancer Center ( P30CA125123 ). Funding Information: We thank Yuxi Chen and Junyan Feng for their assistance with protein expression and purification. We are also grateful to members of the Songyang laboratory for their insightful discussions and technical assistance. Our work was supported by grants from National Key Research and Development Program of China (2017YFA0102801), the National Natural Science Foundation of China (91640119, 81330055, 91749113, and 31570827), Science and Technology Planning Project of Guangdong Province (2015B020228002), Guangzhou Science and Technology Project (201605030012), the NIH (HL131744 and CA211653), the Welch Foundation (Q-1673 and I-1441), and CPRIT RP160462. H.Y. is an Investigator with the Howard Hughes Medical Institute. We would also like to acknowledge the support of the C-BASS core and the Dan L. Duncan Cancer Center (P30CA125123). Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2018",
month = may,
day = "3",
doi = "10.1016/j.molcel.2018.03.032",
language = "English (US)",
volume = "70",
pages = "395--407.e4",
journal = "Molecular cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "3",
}