The emerging determinants of replication fork stability

T Thakar, GL Moldovan - Nucleic acids research, 2021 - academic.oup.com
A universal response to replication stress is replication fork reversal, where the nascent
complementary DNA strands are annealed to form a protective four-way junction allowing …

Signaling pathways regulated by UBR box-containing E3 ligases

JG Kim, HC Shin, T Seo, L Nawale, G Han… - International journal of …, 2021 - mdpi.com
UBR box E3 ligases, also called N-recognins, are integral components of the N-degron
pathway. Representative N-recognins include UBR1, UBR2, UBR4, and UBR5, and they …

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

J Rageul, JJ Park, PP Zeng, EA Lee, J Yang… - Nature …, 2020 - nature.com
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 …

Replisome dysfunction upon inducible TIMELESS degradation synergizes with ATR inhibition to trigger replication catastrophe

JA Patel, C Zezelic, J Rageul, J Saldanha… - Nucleic Acids …, 2023 - academic.oup.com
The structure of DNA replication forks is preserved by TIMELESS (TIM) in the fork protection
complex (FPC) to support seamless fork progression. While the scaffolding role of the FPC to …

The ubiquitin proteasome system in genome stability and cancer

JJ Morgan, LJ Crawford - Cancers, 2021 - mdpi.com
Simple Summary Genomic instability is a major driving force of tumour development and
evolution. Cells have developed sophisticated regulatory systems to preserve the stability of …

The C‐degron pathway eliminates mislocalized proteins and products of deubiquitinating enzymes

CW Yeh, WC Huang, PH Hsu, KH Yeh, LC Wang… - The EMBO …, 2021 - embopress.org
Protein termini are determinants of protein stability. Proteins bearing degradation signals, or
degrons, at their amino‐or carboxyl‐termini are eliminated by the N‐or C‐degron pathways …

Extended DNA-binding interfaces beyond the canonical SAP domain contribute to the function of replication stress regulator SDE2 at DNA replication forks

AS Weinheimer, YT Paung, J Rageul, A Khan… - Journal of Biological …, 2022 - ASBMB
Elevated DNA replication stress causes instability of the DNA replication fork and increased
DNA mutations, which underlies tumorigenesis. The DNA replication stress regulator …

Downregulation of the Arg/N-degron pathway sensitizes cancer cells to chemotherapy in vivo

D Leboeuf, T Abakumova, T Prikazchikova, L Rhym… - Molecular therapy, 2020 - cell.com
The N-degron pathway is an emerging target for anti-tumor therapies, because of its
capacity to positively regulate many hallmarks of cancer, including angiogenesis, cell …

SDE2 is an essential gene required for ribosome biogenesis and the regulation of alternative splicing

J Floro, A Dai, A Metzger, A Mora-Martin… - Nucleic Acids …, 2021 - academic.oup.com
RNA provides the framework for the assembly of some of the most intricate macromolecular
complexes within the cell, including the spliceosome and the mature ribosome. The …

Splicing of branchpoint-distant exons is promoted by Cactin, Tls1 and the ubiquitin-fold-activated Sde2

AT Anil, K Choudhary, R Pandian, P Gupta… - Nucleic Acids …, 2022 - academic.oup.com
Intron diversity facilitates regulated gene expression and alternative splicing. Spliceosomes
excise introns after recognizing their splicing signals: the 5′-splice site (5′ ss) …