DNA Repair: ERCC1, Nucleotide Excision Repair, and Platinum Resistance

Reed, Eddie; Larkins, Teri; Chau, Cindy H.; Figg, William D.

doi:10.1007/978-1-4614-9135-4_18

Cited by 5 publications

(4 citation statements)

References 66 publications

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“…Notably, several genes in the nucleotide excision repair pathway showed signatures of positive selection. One of them encodes the DNA excision repair protein ERCC-1 (or UV hypersensitive 7), which was also identified previously (4) and is reported to function as a component of a structure-specific endonuclease that cleaves on the 5ʹ side of UV photoproducts in DNA (49). In addition to ERCC-1, we identified PSGs that encode the AP endonuclease 2 protein (APEX2), DNA polymerase delta subunit 2 (POLD2), DNA mismatch repair protein MLH1, and DNA repair and recombination protein RAD54 ( SI Appendix , Table S14).…”

Section: Resultsmentioning

confidence: 86%

Genome of Crucihimalaya himalaica , a close relative of Arabidopsis , shows ecological adaptation to high altitude

Zhang

Qiao

Novikova

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

102

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Crucihimalaya himalaica, a close relative ofArabidopsisandCapsella, grows on the Qinghai–Tibet Plateau (QTP) about 4,000 m above sea level and represents an attractive model system for studying speciation and ecological adaptation in extreme environments. We assembled a draft genome sequence of 234.72 Mb encoding 27,019 genes and investigated its origin and adaptive evolutionary mechanisms. Phylogenomic analyses based on 4,586 single-copy genes revealed thatC. himalaicais most closely related toCapsella(estimated divergence 8.8 to 12.2 Mya), whereas both species form a sister clade toArabidopsis thalianaandArabidopsis lyrata, from which they diverged between 12.7 and 17.2 Mya. LTR retrotransposons inC. himalaicaproliferated shortly after the dramatic uplift and climatic change of the Himalayas from the Late Pliocene to Pleistocene. Compared with closely related species,C. himalaicashowed significant contraction and pseudogenization in gene families associated with disease resistance and also significant expansion in gene families associated with ubiquitin-mediated proteolysis and DNA repair. We identified hundreds of genes involved in DNA repair, ubiquitin-mediated proteolysis, and reproductive processes with signs of positive selection. Gene families showing dramatic changes in size and genes showing signs of positive selection are likely candidates forC. himalaica’s adaptation to intense radiation, low temperature, and pathogen-depauperate environments in the QTP. Loss of function at the S-locus, the reason for the transition to self-fertilization ofC. himalaica, might have enabled its QTP occupation. Overall, the genome sequence ofC. himalaicaprovides insights into the mechanisms of plant adaptation to extreme environments.

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Section: Resultsmentioning

confidence: 86%

Genome of Crucihimalaya himalaica , a close relative of Arabidopsis , shows ecological adaptation to high altitude

Zhang

Qiao

Novikova

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

102

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“…DDP is commonly used to treat ovarian cancer. The mechanism of its anticancer action is cytotoxicity by binding to DNA molecules to form a platinum-DNA adduct ( 32 ). γ-H2AX is a DNA damage marker.…”

Section: Resultsmentioning

confidence: 99%

The Hedgehog signaling pathway promotes chemotherapy resistance via multidrug resistance protein 1 in ovarian cancer

Zhang

Cheng

et al. 2020

Oncol Rep

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Various studies have revealed that the Hedgehog (Hh) signaling pathway promotes ovarian cancer invasion, migration and drug resistance. Previous studies by our group have identified a set of genes, including multidrug resistance gene 1 (MDR1), that are regulated by Hh signaling in ovarian cancer. However, the association between Hh signaling activation and MDR1 expression requires further validation. In the present study, reverse transcription-quantitative PCR or western blot assays were used to evaluate the mRNA and protein expression levels of MDR1, Sonic Hh (Shh), glioma-associated oncogene 2 (Gli2), Gli1 and γ-phosphorylated H2A.X variant histone (γ-H2AX). MTT and colony-formation assays were performed to determine the effect of cisplatin (DDP) after inhibiting the Hh pathway in ovarian cancer cells. The results indicated that MDR1, Gli2 and Shh levels were much higher in SK-OV-3 cells with acquired DDP resistance than in native SK-OV-3 cells. ES-2 cells with overexpression of Gli2 were capable of efficiently forming colonies in the presence of low DDP concentrations. By contrast, Gli2 knockdown in SK-OV-3 cells decreased the colony-forming ability under the same concentration of DDP. As determined by MTT assays, knockdown of Gli2 or targeting of the Hh signaling pathway with either Gli-antagonist 61 (GANT61) or cyclopamine, in combination with DDP treatment, diminished the viability of ES-2 and SK-OV-3 cells, whereas Gli2 overexpression increased the viability of ES-2 cells in the presence of DDP. Knockdown of Gli2 or targeting the Hh signaling pathway with GANT61 also increased γ-H2AX levels but decreased the expression of MDR1 in the presence of DDP. MDR1 expression is regulated by the Hh signaling pathway and is likely a downstream transcription factor of Gli2. In conclusion, targeting the Hh signaling pathway increases the sensitivity of ovarian cancer to DDP. MDR1 is a target gene of the Hh signaling pathway and this pathway may affect chemoresistance of ovarian cancer to DDP via MDR1.

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“…It is worth to mention that several essential genes participating in NER process showed positive selection. Such as gene encoding DNA excision repair protein ERCC-1 (or ultraviolet hypersensitive 7), which has been reported to function as a part of a structure-specific endonuclease that cleaves 5′ to UV photoproducts in DNA 33 . And gene encoding DNA damage-binding protein 2, which forms a complex with DDB1 to recognize damaged DNA and initiation of NER process after exposure to UV light 34 .…”

Section: Discussionmentioning

confidence: 99%

Transcriptome sequencing of Crucihimalaya himalaica (Brassicaceae) reveals how Arabidopsis close relative adapt to the Qinghai-Tibet Plateau

Qiao

Qia

Han

et al. 2016

Sci Rep

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The extreme environment of the Qinghai-Tibet Plateau (QTP) provides an ideal natural laboratory for studies on adaptive evolution. Few genome/transcriptome based studies have been conducted on how plants adapt to the environments of QTP compared to numerous studies on vertebrates. Crucihimalaya himalaica is a close relative of Arabidopsis with typical QTP distribution, and is hoped to be a new model system to study speciation and ecological adaptation in extreme environment. In this study, we de novo generated a transcriptome sequence of C. himalaica, with a total of 49,438 unigenes. Compared to five relatives, 10,487 orthogroups were shared by all six species, and 4,286 orthogroups contain putative single copy gene. Further analysis identified 487 extremely significantly positively selected genes (PSGs) in C. himalaica transcriptome. Theses PSGs were enriched in functions related to specific adaptation traits, such as response to radiation, DNA repair, nitrogen metabolism, and stabilization of membrane. These functions are responsible for the adaptation of C. himalaica to the high radiation, soil depletion and low temperature environments on QTP. Our findings indicate that C. himalaica has evolved complex strategies for adapting to the extreme environments on QTP and provide novel insights into genetic mechanisms of highland adaptation in plants.

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DNA Repair: ERCC1, Nucleotide Excision Repair, and Platinum Resistance

Cited by 5 publications

References 66 publications

Genome of Crucihimalaya himalaica , a close relative of Arabidopsis , shows ecological adaptation to high altitude

Genome of Crucihimalaya himalaica , a close relative of Arabidopsis , shows ecological adaptation to high altitude

The Hedgehog signaling pathway promotes chemotherapy resistance via multidrug resistance protein 1 in ovarian cancer

Transcriptome sequencing of Crucihimalaya himalaica (Brassicaceae) reveals how Arabidopsis close relative adapt to the Qinghai-Tibet Plateau

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