DNA repair, Journal Year: 2021, Volume and Issue: 110, P. 103263 - 103263
Published: Dec. 24, 2021
Language: Английский
Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9
Published: Nov. 2, 2021
The maintenance of genome integrity and fidelity is vital for the proper function survival all organisms. Recent studies have revealed that APE2 required to activate an ATR-Chk1 DNA damage response (DDR) pathway in oxidative stress a defined single-strand break (SSB) Xenopus laevis egg extracts. However, it remains unclear whether general regulator DDR mammalian cells. Here, we provide evidence using human pancreatic cancer cells essential ATR activation different stressful conditions including stress, replication double-strand breaks. Fluorescence microscopy analysis shows APE2-knockdown (KD) leads enhanced γH2AX foci increased micronuclei formation. In addition, identified small molecule compound Celastrol as inhibitor specifically compromises binding but not RPA ssDNA 3'-5' exonuclease activity APE1. impairment by extracts highlights physiological significance regulation functionalities integrity. Notably, cell viability assays demonstrate APE2-KD or sensitizes chemotherapy drugs. Overall, propose maintenance.
Language: Английский
Citations
13
Frontiers in Physiology, Journal Year: 2018, Volume and Issue: 9
Published: Nov. 27, 2018
The use of the Xenopus model system has provided diverse contributions to cancer research, not least because striking parallels between tumour pathogenesis and early embryo development. Cell cycle regulation, signalling pathways cell behaviours such as migration are frequently perturbed in cancers; all have been investigated using Xenopus, these developmental events can additionally act an assay for drug development studies. In this mini-review, we focus our discussion primarily on whole models informing biology; date future potential. Insights into immunity, oncogene function visualisation vascular responses during formation achieved with naturally occurring tumours induced-tumour-like-structures (ITLS) Xenopus. Finally, now entering era genetically modified models, harness genome editing techniques recapitulate human disease through creating embryos analogous genetic abnormalities. With speed, versatility accessibility that epitomise system, new range pre-clinical great potential advance mechanistic understanding oncogenesis provide vivo chemotherapeutic
Language: Английский
Citations
15
NAR Cancer, Journal Year: 2023, Volume and Issue: 5(1)
Published: Jan. 11, 2023
Abstract AP endonuclease 2 (APE2, APEX2 or APN2) is an emerging critical protein involved in genome and epigenome integrity. Whereas its catalytic function as a nuclease DNA repair widely accepted, recent studies have elucidated the mechanism of APE2 immune response damage response. Several genome-wide screens identified synthetic lethal target for deficiencies BRCA1, BRCA2 TDP1 cancer cells. Due to overexpression several types, proposed oncogene could serve prognostic marker overall survival treatment. However, it remains be discovered whether how lethality can modulated manipulated therapy target. In this review, we provide current understanding alterations expression cancer, response, mechanisms ATR/Chk1 We also summarize role pathways removal heterogenous complexed 3’-termini MMEJ. Finally, updated perspective on may targeted future directions biology.
Language: Английский
Citations
5
Methods in molecular biology, Journal Year: 2019, Volume and Issue: unknown, P. 161 - 172
Published: Jan. 1, 2019
Language: Английский
Citations
13
Biochemical Journal, Journal Year: 2019, Volume and Issue: 476(24), P. 3791 - 3804
Published: Dec. 6, 2019
Oxidative DNA damage represents one of the most abundant lesions. It remains unclear how repair and response (DDR) pathways are co-ordinated regulated following oxidative stress. While XRCC1 has been implicated in repair, it unknown exactly is repaired sensed by XRCC1. In this communication, we have demonstrated evidence that dispensable for ATR-Chk1 DDR pathway stress Xenopus egg extracts. Whereas APE2 essential SSB not required defined gapped plasmids with a 5'-OH or 5'-P terminus, suggesting may contribute to via different mechanisms. Neither Polymerase beta nor alpha important structure. Nonetheless, Our observations suggest distinct roles genome integrity
Language: Английский
Citations
13
genesis, Journal Year: 2017, Volume and Issue: 55(1-2)
Published: Jan. 1, 2017
Abstract Cell‐free cytoplasmic extracts prepared from Xenopus eggs and embryos have for decades provided a biochemical system with which to interrogate complex cell biological processes in vitro . Recently, the application of microfabrication microfluidic strategies biology has narrowed gap between vivo studies by enabling formation cell‐size compartments containing functional cytoplasm. These approaches provide numerous advantages over traditional experiments performed test tube. Most notably, cell‐free cytoplasm is confined using two‐ or three‐dimensional boundary, mimics natural configuration cell. This strategy enables characterization spatial organization cell, role that boundaries play regulating intracellular assembly function. In this review, we describe marriage confinement technologies generate synthetic cell‐like systems, recent insights they enabled, promise hold future scientific discovery.
Language: Английский
Citations
12
Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9
Published: Dec. 7, 2021
The maintenance of genome stability requires dedicated DNA repair processes and pathways that are essential for the faithful duplication propagation chromosomes. These mechanisms counteract potentially deleterious impact frequent genotoxic challenges faced by cells from both exogenous endogenous agents. Intrinsic to these mechanisms, have an arsenal protein factors can be utilised promote in response lesions. Orchestration within various cellular is performed, part, post-translational modifications, such as phosphorylation, ubiquitin, SUMO other ubiquitin-like modifiers (UBLs). In this review, we firstly explore recent advances tools identifying involved ubiquitin signaling pathways. We then expand on evaluating growing repertoire proteomic, biochemical structural techniques available further understand mechanistic basis which complex modifications regulate repair. Together, provide a snapshot range methods now investigate decode how maintain mammalian cells.
Language: Английский
Citations
5
DNA, Journal Year: 2023, Volume and Issue: 3(2), P. 109 - 118
Published: June 6, 2023
Human genomic DNA contains a number of diverse repetitive sequence motifs, often identified as fragile sites leading to genetic instability. Among them, expansion events occurring at triplet repeats have been extensively studied due their association with neurological disorders, including Huntington’s disease (HD). In the case HD, expanded CAG in HTT gene are thought cause onset. The is believed be triggered by emergence stem-loops composed repeats, while underlying molecular mechanisms largely unknown. Therefore, identifying proteins recruited on such stem loops would useful understand instability repeats. We previously developed plasmid pull-down methodology that captures specifically assembled any interest using nuclear extracts. Analysis Mass Spectrometry revealed among bound stem-loop many turned out belong repair pathways. expect our data set represent entry point for design assays allowing explored.
Language: Английский
Citations
1
CRC Press eBooks, Journal Year: 2022, Volume and Issue: unknown, P. 13 - 24
Published: March 17, 2022
Extracts prepared from the eggs of African clawed frog, Xenopus laevis, have been instrumental in elucidating mechanisms that underlie vertebrate cell division control and DNA replication. Egg extracts unique capacity to undergo cycle transitions vitro, enabling biochemical dissection pathways involved. The also contain components sufficient generate thousands nuclei per microliter through stockpiles essential replication factors substrates. Although critical early applications this experimental system study occurred nearly 40 years ago, vitro model continues be relevant today: creative new are constantly being devised. In chapter, history current powerful discussed.
Language: Английский
Citations
2
Methods, Journal Year: 2021, Volume and Issue: 194, P. 75 - 82
Published: Jan. 22, 2021
Language: Английский
Citations
1