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Crosstalk between CST and RPA regulates RAD51 activity during replication stress

Author

Listed:
  • Kai-Hang Lei

    (National Taiwan University)

  • Han-Lin Yang

    (National Taiwan University)

  • Hao-Yen Chang

    (National Taiwan University)

  • Hsin-Yi Yeh

    (National Taiwan University)

  • Dinh Duc Nguyen

    (Loyola University Chicago Stritch School of Medicine)

  • Tzu-Yu Lee

    (National Taiwan University)

  • Xinxing Lyu

    (Loyola University Chicago Stritch School of Medicine)

  • Megan Chastain

    (Washington State University)

  • Weihang Chai

    (Loyola University Chicago Stritch School of Medicine)

  • Hung-Wen Li

    (National Taiwan University)

  • Peter Chi

    (National Taiwan University
    Academia Sinica)

Abstract

Replication stress causes replication fork stalling, resulting in an accumulation of single-stranded DNA (ssDNA). Replication protein A (RPA) and CTC1-STN1-TEN1 (CST) complex bind ssDNA and are found at stalled forks, where they regulate RAD51 recruitment and foci formation in vivo. Here, we investigate crosstalk between RPA, CST, and RAD51. We show that CST and RPA localize in close proximity in cells. Although CST stably binds to ssDNA with a high affinity at low ionic strength, the interaction becomes more dynamic and enables facilitated dissociation at high ionic strength. CST can coexist with RPA on the same ssDNA and target RAD51 to RPA-coated ssDNA. Notably, whereas RPA-coated ssDNA inhibits RAD51 activity, RAD51 can assemble a functional filament and exhibit strand-exchange activity on CST-coated ssDNA at high ionic strength. Our findings provide mechanistic insights into how CST targets and tethers RAD51 to RPA-coated ssDNA in response to replication stress.

Suggested Citation

  • Kai-Hang Lei & Han-Lin Yang & Hao-Yen Chang & Hsin-Yi Yeh & Dinh Duc Nguyen & Tzu-Yu Lee & Xinxing Lyu & Megan Chastain & Weihang Chai & Hung-Wen Li & Peter Chi, 2021. "Crosstalk between CST and RPA regulates RAD51 activity during replication stress," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26624-x
    DOI: 10.1038/s41467-021-26624-x
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    References listed on IDEAS

    as
    1. Neal F. Lue & Jamie Chan & Woodring E. Wright & Jerard Hurwitz, 2014. "The CDC13-STN1-TEN1 complex stimulates Pol α activity by promoting RNA priming and primase-to-polymerase switch," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
    2. Liuh-Yow Chen & Sophie Redon & Joachim Lingner, 2012. "The human CST complex is a terminator of telomerase activity," Nature, Nature, vol. 488(7412), pages 540-544, August.
    3. Jennifer M. Mason & Yuen-Ling Chan & Ralph W. Weichselbaum & Douglas K. Bishop, 2019. "Non-enzymatic roles of human RAD51 at stalled replication forks," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
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    Cited by:

    1. Guangxue Liu & Jimin Li & Boxue He & Jiaqi Yan & Jingyu Zhao & Xuejie Wang & Xiaocong Zhao & Jingyan Xu & Yeyao Wu & Simin Zhang & Xiaoli Gan & Chun Zhou & Xiangpan Li & Xinghua Zhang & Xuefeng Chen, 2023. "Bre1/RNF20 promotes Rad51-mediated strand exchange and antagonizes the Srs2/FBH1 helicases," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Rishi Kumar Jaiswal & Kai-Hang Lei & Megan Chastain & Yuan Wang & Olga Shiva & Shan Li & Zhongsheng You & Peter Chi & Weihang Chai, 2023. "CaMKK2 and CHK1 phosphorylate human STN1 in response to replication stress to protect stalled forks from aberrant resection," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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