Strand annealing and motor driven activities of SMARCAL1 and ZRANB3 are stimulated by RAD51 and the paralog complex DOI Creative Commons

Swagata Halder,

Lepakshi Ranjha, Angelo Taglialatela

et al.

Nucleic Acids Research, Journal Year: 2022, Volume and Issue: 50(14), P. 8008 - 8022

Published: July 8, 2022

Abstract SMARCAL1, ZRANB3 and HLTF are required for the remodeling of replication forks upon stress to promote genome stability. RAD51, along with RAD51 paralog complex, were also found have recombination-independent functions in fork reversal, yet underlying mechanisms remained unclear. Using reconstituted reactions, we build previous data show that unequal biochemical capacities, explaining why they non-redundant functions. SMARCAL1 uniquely anneals RPA-coated ssDNA, which depends on its direct interaction RPA, but not ATP. ZRANB3, efficiently employ ATPase driven translocase activity rezip RPA-covered bubbled DNA, was proposed mimic elements reversal. In contrast, efficient branch migration occurs downstream remodeling. We low concentrations RAD51B–RAD51C–RAD51D–XRCC2 (BCDX2), directly stimulate motor-driven activities HLTF, interplay is underpinned by physical interactions. Our provide a possible mechanism cellular experiments implicating BCDX2

Language: Английский

Role of Oxidative Stress in the Occurrence, Development, and Treatment of Breast Cancer DOI Creative Commons
Rui Dong, Jing Wang,

Rijian Guan

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(1), P. 104 - 104

Published: Jan. 17, 2025

Breast cancer is one of the most prevalent cancers worldwide. Recent studies have increasingly emphasized role oxidative stress in initiation and progression breast cancer. This article reviews how imbalance influences occurrence advancement cancer, elucidating intricate mechanisms through which reactive oxygen species (ROS) operate this context their potential therapeutic applications. By highlighting these critical insights, review aims to enhance our understanding as a target for innovative strategies management

Language: Английский

Citations

3
CARM1 regulates replication fork speed and stress response by stimulating PARP1 DOI Creative Commons

Marie‐Michelle Genois,

Jean‐Philippe Gagné, Takaaki Yasuhara

et al.

Molecular Cell, Journal Year: 2021, Volume and Issue: 81(4), P. 784 - 800.e8

Published: Jan. 9, 2021

Language: Английский

Citations

83
To skip or not to skip: choosing repriming to tolerate DNA damage DOI
Annabel Quinet,

Stephanie Tirman,

Emily Cybulla

et al.

Molecular Cell, Journal Year: 2021, Volume and Issue: 81(4), P. 649 - 658

Published: Jan. 29, 2021

Language: Английский

Citations

80
Two replication fork remodeling pathways generate nuclease substrates for distinct fork protection factors DOI Creative Commons
Wenpeng Liu, Archana Krishnamoorthy,

Runxiang Zhao

et al.

Science Advances, Journal Year: 2020, Volume and Issue: 6(46)

Published: Nov. 13, 2020

At least two groups of fork protection factors work downstream RAD51-dependent remodeling pathways.

Language: Английский

Citations

72
Exploiting replication gaps for cancer therapy DOI Creative Commons
Ke Cong, Sharon B. Cantor

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(13), P. 2363 - 2369

Published: May 13, 2022

Language: Английский

Citations

67
Excessive reactive oxygen species induce transcription-dependent replication stress DOI Creative Commons
Martin Andrš, Henriette Stoy, Barbora Boleslavska

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: March 30, 2023

Elevated levels of reactive oxygen species (ROS) reduce replication fork velocity by causing dissociation the TIMELESS-TIPIN complex from replisome. Here, we show that ROS generated exposure human cells to ribonucleotide reductase inhibitor hydroxyurea (HU) promote reversal in a manner dependent on active transcription and formation co-transcriptional RNA:DNA hybrids (R-loops). The frequency R-loop-dependent stalling events is also increased after TIMELESS depletion or partial inhibition replicative DNA polymerases aphidicolin, suggesting this phenomenon due global slowdown. In contrast, arrest caused HU-induced deoxynucleotides does not induce but, if allowed persist, leads extensive R-loop-independent breakage during S-phase. Our work reveals link between oxidative stress transcription-replication interference causes genomic alterations recurrently found cancer.

Language: Английский

Citations

42
LINC01088 prevents ferroptosis in glioblastoma by enhancing SLC7A11 via HLTF/USP7 axis DOI Creative Commons
Yujie Zhou,

Zhen Zhao,

Jiang Cheng

et al.

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(3)

Published: Feb. 25, 2025

Glioblastoma multiforme (GBM)is a highly aggressive malignancy of the central nervous system characterized by poor survival rates. Ferroptosis, an iron-dependent cell death pathway, is promising therapeutic target for GBM. However, current treatments targeting pathways have not yielded expected results. Long noncoding RNAs (lncRNAs) been implicated in tumour proliferation, however, their role ferroptosis GBM remains underexplored. This study investigated interplay between lncRNA LINC01088 and to identify novel strategies. We conducted gain- loss-of-function studies assess impact on tumourigenesis both vitro vivo. Bioinformatics, dual-luciferase reporter assays, chromatin immunoprecipitation, RNA pulldown, mass spectrometry, immunoprecipitation (RIP), transcriptome sequencing were utilized elucidate mechanisms underlying expression its downstream effects ferroptosis. The transcription factor specificity protein 1 (SP1) was identified as promoter transcription, which facilitated progression. found inhibit promote malignancy. Mechanistically, stabilized HLTF enhancing interaction with USP7 preventing ubiquitin-mediated degradation. stabilization led upregulation SLC7A11, inhibits Rescue experiments confirmed that altering levels reversed ferroptotic phenotypes associated modulation. revealed SP1/LINC01088/HLTF/USP7/SLC7A11 axis regulates GBM, highlighting potential ferroptosis-dependent treatment. transcriptionally upregulated SP1. acts scaffold platform bind HLTF. USP7, deubiquitinating enzyme HLTF, participates inhibiting ubiquitin-proteasome degradation upregates cells inhibited.

Language: Английский

Citations

1
PCAF-Mediated Histone Acetylation Promotes Replication Fork Degradation by MRE11 and EXO1 in BRCA-Deficient Cells DOI Creative Commons

Jae Jin Kim,

Seo Yun Lee,

Ji Hye Choi

et al.

Molecular Cell, Journal Year: 2020, Volume and Issue: 80(2), P. 327 - 344.e8

Published: Sept. 22, 2020

Language: Английский

Citations

59
The Hammer and the Dance of Cell Cycle Control DOI Creative Commons
Ανδρέας Παναγόπουλος, Matthias Altmeyer

Trends in Biochemical Sciences, Journal Year: 2020, Volume and Issue: 46(4), P. 301 - 314

Published: Dec. 2, 2020

Cell cycle checkpoints secure ordered progression from one cell phase to the next. They are important signal stress and DNA lesions stop when severe problems occur. Recent work suggests, however, that control machinery responds in more subtle sophisticated ways cells faced with naturally occurring challenges, such as replication impediments associated endogenous stress. Instead of following a go approach, use fine-tuned deceleration brake release mechanisms under ataxia telangiectasia Rad3-related protein kinase (ATR) checkpoint 1 (CHK1) flexibly adapt their program changing conditions. We highlight emerging examples intrinsic regulation discuss physiological clinical relevance.

Language: Английский

Citations

53
PrimPol‐mediated repriming facilitates replication traverse of DNA interstrand crosslinks DOI Creative Commons
Daniel González‐Acosta, Elena Blanco‐Romero, Patricia Ubieto‐Capella

et al.

The EMBO Journal, Journal Year: 2021, Volume and Issue: 40(14)

Published: June 15, 2021

Abstract DNA interstrand crosslinks (ICLs) induced by endogenous aldehydes or chemotherapeutic agents interfere with essential processes such as replication and transcription. ICL recognition repair the Fanconi Anemia pathway require formation of an X‐shaped structure that may arise from convergence two forks at crosslink traversing lesion a single fork. Here, we report traverse strictly requires repriming events downstream lesion, which are carried out PrimPol, second primase‐polymerase identified in mammalian cells after Polα/Primase. The recruitment PrimPol to vicinity ICLs depends on its interaction RPA, but not FANCM translocase BLM/TOP3A/RMI1‐2 (BTR) complex also participate traverse. Genetic ablation PRIMPOL makes more dependent fork mechanism initiate repair, KO mice display hypersensitivity ICL‐inducing drugs. These results open possibility targeting activity enhance efficacy chemotherapy based crosslinking agents.

Language: Английский

Citations

53