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Lee, Eun A
유전체 항상성 연구단
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SDE2 integrates into the TIMELESS-TIPIN complex to protect stalled replication forks

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Title
SDE2 integrates into the TIMELESS-TIPIN complex to protect stalled replication forks
Author(s)
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
Publication Date
2020-12
Journal
NATURE COMMUNICATIONS, v.11, no.1, pp.5495
Publisher
NATURE PUBLISHING GROUP
Abstract
© 2020, The Author(s). 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
URI
https://pr.ibs.re.kr/handle/8788114/7518
DOI
10.1038/s41467-020-19162-5
ISSN
2041-1723
Appears in Collections:
Center for Genomic Integrity(유전체 항상성 연구단) > 1. Journal Papers (저널논문)
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