Cited by APE1 recruits ATRIP to ssDNA in an RPA-independent manner to promote the ATR DNA damage response

APE1 recruits ATRIP to ssDNA in an RPA-dependent and -independent manner to promote the ATR DNA damage response DOI

Yunfeng Lin, Jia Li, Haichao Zhao

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: May 22, 2023

Cells have evolved the DNA damage response (DDR) pathways in to replication stress or damage. In ATR-Chk1 DDR pathway, it has been proposed that ATR is recruited RPA-coated single-stranded (ssDNA) by direct ATRIP-RPA interaction. However, remains elusive how ATRIP ssDNA an RPA-independent manner. Here, we provide evidence APE1 directly associates recruit onto fashion. The N-terminal motif within required and sufficient for APE1-ATRIP interaction vitro distinct recruitment pathway activation Xenopus egg extracts. addition, with RPA70 RPA32 via two motifs. Taken together, our suggests recruits RPA-dependent -independent manner pathway.

Language: Английский

Citations

Distinct regulation of ATM signaling by DNA single-strand breaks and APE1 DOI

Haichao Zhao, Jia Li, Zhongsheng You

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 7, 2024

Abstract In response to DNA double-strand breaks or oxidative stress, ATM-dependent damage (DDR) is activated maintain genome integrity. However, it remains elusive whether and how single-strand (SSBs) activate ATM. Here, we provide direct evidence in Xenopus egg extracts that ATM-mediated DDR by a defined SSB structure. Our mechanistic studies reveal APE1 promotes the SSB-induced ATM through exonuclease activity recruitment sites. protein can form oligomers absence of directly stimulate kinase vitro. findings distinct mechanisms activation SSBs eukaryotic systems identify as activator kinase.

Language: Английский

Citations

Novel Processes Associated with the Repair of Interstrand Cross-Links Derived from Abasic Sites in Duplex DNA: Roles for the Base Excision Repair Glycosylase NEIL3 and the SRAP Protein HMCES DOI

Nathan E. Price,

Kent S. Gates

Chemical Research in Toxicology, Journal Year: 2024, Volume and Issue: 37(2), P. 199 - 207

Published: Jan. 10, 2024

Recent studies have defined a novel pathway for the repair of interstrand cross-links derived from reaction an adenine residue with apurinic/apyrimidinic (AP) site on opposing strand DNA (dA-AP ICL). Stalling replication fork at dA-AP ICL triggers TRAIP-dependent ubiquitylation CMG helicase that recruits base excision glycosylase NEIL3 to lesion. unhooks regenerate native one and AP other strand. Covalent capture abasic by SRAP protein HMCES protects against genomic instability would result cleavage in context single-stranded fork. After synthesis moves HMCES-AP adduct into double-stranded DNA, DNA–protein cross-link is resolved nonproteolytic mechanism involving dissociation thiazolidine attachment. The duplex then repaired pathway.

Language: Английский

Citations

Role of Base Excision Repair Pathway in the Processing of Complex DNA Damage Generated by Oxidative Stress and Anticancer Drugs DOI

Yeldar Baiken,

Damira Kanayeva, Sabira Taipakova

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 8

Published: Jan. 22, 2021

Chemical alterations in DNA induced by genotoxic factors can have a complex nature such as bulky adducts, interstrand cross-links (ICLs), and clustered lesions (including double-strand breaks, DSB). Complex damage (CDD) has character/structure compared to singular like randomly distributed abasic sites, deaminated, alkylated, oxidized bases. CDD is thought be critical since they are more challenging repair than lesions. Although naturally constitutes relatively minor fraction of the overall free radicals, cross-linking agents, ionizing radiation, if left unrepaired, these cause number serious consequences, gross chromosomal rearrangements genome instability. If not tightly controlled, ICLs bi-stranded bases via excision will either inhibit initial steps or produce persistent breaks consequently lethal for cells. Biochemical genetic evidences indicate that removal requires concurrent involvement distinct pathways including poly(ADP-ribose) polymerase (PARP)-mediated strand break repair, base (BER), nucleotide incision (NIR), global transcription coupled (GG-NER TC-NER, respectively), mismatch (MMR), homologous recombination (HR), non-homologous end joining (NHEJ), translesion synthesis (TLS) pathways. In this review, we describe role glycosylase-mediated BER pathway

Language: Английский

Citations

DNA polymerase θ-mediated repair of high LET radiation-induced complex DNA double-strand breaks DOI

Geunil Yi,

Yubin Sung,

Chan-Woo Kim

et al.

Nucleic Acids Research, Journal Year: 2023, Volume and Issue: 51(5), P. 2257 - 2269

Published: Feb. 20, 2023

Abstract DNA polymerase θ (POLQ) is a unique that able to perform microhomology-mediated end-joining as well translesion synthesis (TLS) across an abasic (AP) site and thymine glycol (Tg). However, the biological significance of TLS activity currently unknown. Herein we provide evidence POLQ plays critical role in repairing complex double-strand breaks (DSBs) induced by high linear energy transfer (LET) radiation. Radiotherapy with LET radiation such carbon ions leads more deleterious effects than corresponding doses low X-rays. High LET-induced DSBs are considered be complex, carrying additional damage AP Tg close proximity DSB sites. it not clearly understood how processed mammalian cells. We demonstrated genetic disruption results increase chromatid enhanced cellular sensitivity following treatment At biochemical level, was bypass during anneal two single-stranded tails when lesions were located outside microhomology. This study offers directly involved repair DSBs.

Language: Английский

Citations

NEIL3-mediated proteasomal degradation facilitates the repair of cisplatin-induced DNA damage in human cells DOI

Umit Aliyaskarova,

Yeldar Baiken,

Flore Renaud

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: March 30, 2023

Anti-neoplastic effect of DNA cross-linking agents such as cisplatin, mitomycin C, and psoralen is attributed to their ability induce interstrand cross-links (ICLs), which block replication, transcription, linear repair pathways by preventing strand separation trigger apoptosis. It generally agreed that the Fanconi anemia (FA) pathway orchestrates removal ICLs combined actions various pathways. Recently, attention has been focused on NEIL3-initiated base excision resolve psoralen- abasic site-induced in an FA-independent manner. Intriguingly, overexpression NEIL3 associated with chemo-resistance poor prognosis many solid tumors. Here, using loss- gain-of-function approaches, we demonstrate confers resistance cisplatin participates cisplatin-DNA adducts. Proteomic studies reveal protein interacts 26S proteasome a cisplatin-dependent mediates proteasomal degradation WRNIP1, involved early step ICL repair. We propose ICL-stalled replication fork recruitment ensure timely transition from lesion recognition via early-step vanguard proteins.

Language: Английский

Citations

Deficiency of NEIL3 Enhances the Chemotherapy Resistance of Prostate Cancer DOI

Yiwei Wang,

Liuyue Xu,

Shanshan Shi

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(8), P. 4098 - 4098

Published: April 15, 2021

Acquired treatment resistance is an important cause of death in prostate cancer, and this study aimed to explore the mechanisms chemotherapy cancer. We employed castration-resistant cancer (CRPC), neuroendocrine (NEPC), chemotherapy-resistant datasets screen for potential target genes. The Cancer Genome Atlas (TCGA) was used detect correlation between genes prognosis clinical characteristics. Nei endonuclease VIII-like 3 (NEIL3) knockdown cell lines were constructed with RNA interference. Prostate cells treated enzalutamide androgen deprivation therapy (ADT) model, docetaxel cisplatin model. Apoptosis cycle examined using flow cytometry. sequencing western blotting performed Duke University 145 (DU145) line possible mechanisms. TCGA dataset demonstrated that high NEIL3 associated a T stage Gleason score, indicated possibility lymph node metastasis, but good prognosis. models showed loss could promote (but not ADT resistance) (PCa). Flow cytometry revealed PCa inhibit apoptosis arrest under treatment. changes expression neuroendocrine-related Further significantly phosphorylation ATR serine/threonine kinase (ATR) ATM (ATM) chemotherapy, thus initiating downstream pathways related DNA repair. In summary, promotes may serve as diagnostic marker patients.

Language: Английский

Citations

NEIL3 Mediates Lung Cancer Progression and Modulates PI3K/AKT/mTOR Signaling: A Potential Therapeutic Target DOI

Hongbo Huang, Qingwang Hua

International Journal of Genomics, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 17

Published: April 30, 2022

Background. Nei endonuclease VIII-like 3 (NEIL3) is widely involved in pathophysiological processes of the body; however, its role lung cancer has not been conclusively determined. Objective. This study aimed at exploring NEIL3 cancer. Methods. The public data used this were downloaded from Cancer Genome Atlas (TCGA) database. “Limma” R was for analysis differentially expressed genes. Clinical correlations and prognostic analyses performed using survival package R. proliferative abilities cells evaluated by CCK8 colony formation assays while their invasive migration assessed transwell wound healing assays. Quantitative real-time PCR (qRT-PCR) western blot utilized to detect RNA protein levels. Biological differences between groups determined gene set enrichment (GSEA). Tumor Immune Dysfunction Exclusion (TIDE) as well Genomics Drug Sensitivity (GDSC) immunotherapeutic chemotherapeutic sensitivity analyses. Results. upregulated NSCLC tissues cell lines, implying that it initiation progression. correlation showed associated with worse clinical features (stage T N classifications) poor outcomes. In vitro, significantly enhanced proliferation, invasion, migration. GSEA indicated might be PI3K/AKT/mTOR, G2/M checkpoints, E2F target pathways. Inhibition suppressed cyclinD1 p-AKT levels; had no effects on AKT levels, indicating can partially activate PI3K/AKT/mTOR signaling pathway. predicted result TIDE nonresponders elevated Moreover, there a positive levels chemosensitivity cisplatin paclitaxel. Conclusion. general, mediates progression affects immunotherapy chemotherapy; therefore, potential molecular treatment.

Language: Английский

Citations

Biological Functions of the DNA Glycosylase NEIL3 and Its Role in Disease Progression Including Cancer DOI

Lang Chen, Xuan Huan,

Xidan Gao

et al.

Cancers, Journal Year: 2022, Volume and Issue: 14(23), P. 5722 - 5722

Published: Nov. 22, 2022

The accumulation of oxidative DNA base damage can severely disrupt the integrity genome and is strongly associated with development cancer. glycosylase critical enzyme that initiates excision repair (BER) pathway, recognizing excising damaged bases. Nei endonuclease VIII-like 3 (NEIL3) an emerging essential in maintaining stability. With in-depth study structure function NEIL3, we found it has properties related to process repair. For example, not only prefers single-stranded (ssDNA), G-quadruplex interstrand crosslinks (ICLs), but also participates maintenance replication fork stability telomere integrity. In addition, NEIL3 progression cancers cardiovascular neurological diseases, incredibly significantly overexpressed cancers, may become independent prognostic marker for cancer patients. Interestingly, circNEIL3, a circular RNA exon-encoded origin by promotes multiple cancers. this review, have summarized characteristics damage. We focused on circNEIL3 development, prognosis.

Language: Английский

Citations

Transcriptional factor MAZ promotes cisplatin-induced DNA damage repair in lung adenocarcinoma by regulating NEIL3 DOI

Tao Wang, Xu Zhu, Kai Wang

et al.

Pulmonary Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 80, P. 102217 - 102217

Published: April 28, 2023

Language: Английский

Citations