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

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 () and Hyungjin Kim ()
Additional contact information
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
Jung-Eun Yeo: Institute for Basic Science
Hyungjin Kim: State University of New York at Stony Brook, Stony Brook

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-19162-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19162-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-19162-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().