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SDE2 integrates into the TIMELESS-TIPIN complex to protect stalled replication forks

Author

Listed:
  • Julie Rageul

    (State University of New York at Stony Brook, Stony Brook)

  • Jennifer J. Park

    (State University of New York at Stony Brook, Stony Brook)

  • Ping Ping Zeng

    (State University of New York at Stony Brook, Stony Brook)

  • Eun-A Lee

    (Institute for Basic Science)

  • Jihyeon Yang

    (Institute for Basic Science)

  • Sunyoung Hwang

    (Institute for Basic Science)

  • Natalie Lo

    (State University of New York at Stony Brook, Stony Brook)

  • Alexandra S. Weinheimer

    (State University of New York at Stony Brook, Stony Brook)

  • Orlando D. Schärer

    (Institute for Basic Science
    School of Life Sciences, Ulsan National Institute of Science and Technology)

  • Jung-Eun Yeo

    (Institute for Basic Science)

  • Hyungjin Kim

    (State University of New York at Stony Brook, Stony Brook
    Renaissance School of Medicine at Stony Brook University, Stony Brook)

Abstract

Protecting replication fork integrity during DNA replication is essential for maintaining genome stability. Here, we report that SDE2, a PCNA-associated protein, plays a key role in maintaining active replication and counteracting replication stress by regulating the replication fork protection complex (FPC). SDE2 directly interacts with the FPC component TIMELESS (TIM) and enhances its stability, thereby aiding TIM localization to replication forks and the coordination of replisome progression. Like TIM deficiency, knockdown of SDE2 leads to impaired fork progression and stalled fork recovery, along with a failure to activate CHK1 phosphorylation. Moreover, loss of SDE2 or TIM results in an excessive MRE11-dependent degradation of reversed forks. Together, our study uncovers an essential role for SDE2 in maintaining genomic integrity by stabilizing the FPC and describes a new role for TIM in protecting stalled replication forks. We propose that TIM-mediated fork protection may represent a way to cooperate with BRCA-dependent fork stabilization.

Suggested Citation

  • Julie Rageul & Jennifer J. Park & Ping Ping Zeng & Eun-A Lee & Jihyeon Yang & Sunyoung Hwang & Natalie Lo & Alexandra S. Weinheimer & Orlando D. Schärer & Jung-Eun Yeo & Hyungjin Kim, 2020. "SDE2 integrates into the TIMELESS-TIPIN complex to protect stalled replication forks," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19162-5
    DOI: 10.1038/s41467-020-19162-5
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    Cited by:

    1. Martin Andrs & Henriette Stoy & Barbora Boleslavska & Nagaraja Chappidi & Radhakrishnan Kanagaraj & Zuzana Nascakova & Shruti Menon & Satyajeet Rao & Anna Oravetzova & Jana Dobrovolna & Kalpana Surend, 2023. "Excessive reactive oxygen species induce transcription-dependent replication stress," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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