The ERCC1 and ERCC4 (XPF) genes and gene products

Manandhar, Mandira; Boulware, Karen S.; Wood, Richard D.

doi:10.1016/j.gene.2015.06.026

Cited by 123 publications

(92 citation statements)

References 121 publications

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“…In this process, the SLX4 protein serves as a scaffold that coordinates the action of several structure-specific endonucleases including XPF-ERCC1, MUS81-EME1, and SLX1 [45, 47, 48]. The involvement of XPF-ERCC1 has been clearly demonstrated[49, 50] and cells deficient in these proteins are acutely hypersensitive to interstrand cross-linking agents [44, 51–54]. The identity of other endonucleases that make incisions during cross-link repair, and the circumstances under which they become involved, remains under investigation [45, 48, 51, 52, 55–58].…”

Section: Replication-dependent Cross-link Repairmentioning

confidence: 99%

A role for the base excision repair enzyme NEIL3 in replication-dependent repair of interstrand DNA cross-links derived from psoralen and abasic sites

et al. 2017

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Interstrand DNA-DNA cross-links are highly toxic lesions that are important in medicinal chemistry, toxicology, and endogenous biology. In current models of replication-dependent repair, stalling of a replication fork activates the Fanconi anemia pathway and cross-links are “unhooked” by the action of structure-specific endonucleases such as XPF-ERCC1 that make incisions flanking the cross-link. This process generates a double-strand break, which must be subsequently repaired by homologous recombination. Recent work provided evidence for a new, incision-independent unhooking mechanism involving intrusion of a base excision repair (BER) enzyme, NEIL3, into the world of cross-link repair. The evidence suggests that the glycosylase action of NEIL3 unhooks interstrand cross-links derived from an abasic site or the psoralen derivative trioxsalen. If the incision-independent NEIL3 pathway is blocked, repair reverts to the incision-dependent route. In light of the new model invoking participation of NEIL3 in cross-link repair, we consider the possibility that various BER glycosylases or other DNA-processing enzymes might participate in the unhooking of chemically diverse interstrand DNA cross-links.

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Section: Replication-dependent Cross-link Repairmentioning

confidence: 99%

A role for the base excision repair enzyme NEIL3 in replication-dependent repair of interstrand DNA cross-links derived from psoralen and abasic sites

et al. 2017

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“…The ten subunits of TFIIH form a core initiation factor for basal transcription of all mRNAs, for example, and XPG also has a transcription-related function [4–6]. ERCC1-XPF participates in some homologous recombination reactions and in crosslink repair [7]. Consequently, complete disruption of some NER components is incompatible with cellular survival or embryonic development (for example, TFIIH subunits or RPA), while perinatal lethality occurs following disruption of other components (ERCC1, XPF, XPG).…”

Section: Introductionmentioning

confidence: 99%

Transcriptional consequences of XPA disruption in human cell lines

et al. 2017

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Nucleotide excision repair (NER) in mammalian cells requires the xeroderma pigmentosum group A protein (XPA) as a core factor. Remarkably, XPA and other NER proteins have been detected by chromatin immunoprecipitation at some active promoters, and NER deficiency is reported to influence the activated transcription of selected genes. However, the global influence of XPA on transcription in human cells has not been determined. We analyzed the human transcriptome by RNA sequencing (RNA-Seq). We first confirmed that XPA is confined to the cell nucleus even in the absence of external DNA damage, in contrast to previous reports that XPA is normally resident in the cytoplasm and is imported following DNA damage. We then analyzed four genetically matched human cell line pairs deficient or proficient in XPA. Of the ∼14,000 genes transcribed in each cell line, 325 genes (2%) had a significant XPA-dependent directional change in gene expression that was common to all four pairs (with a false discovery rate of 0.05). These genes were enriched in pathways for the maintenance of mitochondria. Only 27 common genes were different by more than 1.5-fold. The most significant hits were AKR1C1 and AKR1C2, involved in steroid hormone metabolism. AKR1C2 protein was lower in all of the immortalized XPA-deficient cells. Retinoic acid treatment led to modest XPA-dependent activation of some genes with transcription-related functions. We conclude that XPA status does not globally influence human gene transcription. However, XPA significantly influences expression of a small subset of genes important for mitochondrial functions and steroid hormone metabolism. The results may help explain defects in neurological function and sterility in individuals with xeroderma pigmentosum.

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“…Xpf participates in several DNA repair pathways, including homologous recombination, NER and the Fanconi pathway (Manandhar et al, 2015), which might explain why its role is so fundamental for phagocytic growth. We can only speculate as to the mechanism responsible for causing DNA damage.…”

Section: Resultsmentioning

confidence: 99%

Xpf suppresses the mutagenic consequences of phagocytosis in Dictyostelium

Pontel

Langenick

Rosado

et al. 2016

Journal of Cell Science

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As time passes, mutations accumulate in the genomes of all living organisms. These changes promote genetic diversity, but also precipitate ageing and the initiation of cancer. Food is a common source of mutagens, but little is known about how nutritional factors cause lasting genetic changes in the consuming organism. Here, we describe an unusual genetic interaction between DNA repair in the unicellular amoeba Dictyostelium discoideum and its natural bacterial food source. We found that Dictyostelium deficient in the DNA repair nuclease Xpf (xpf−) display a severe and specific growth defect when feeding on bacteria. Despite being proficient in the phagocytosis and digestion of bacteria, over time, xpf− Dictyostelium feeding on bacteria cease to grow and in many instances die. The Xpf nuclease activity is required for sustained growth using a bacterial food source. Furthermore, the ingestion of this food source leads to a striking accumulation of mutations in the genome of xpf− Dictyostelium. This work therefore establishes Dictyostelium as a model genetic system to dissect nutritional genotoxicity, providing insight into how phagocytosis can induce mutagenesis and compromise survival fitness.

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The ERCC1 and ERCC4 (XPF) genes and gene products

Cited by 123 publications

References 121 publications

A role for the base excision repair enzyme NEIL3 in replication-dependent repair of interstrand DNA cross-links derived from psoralen and abasic sites

A role for the base excision repair enzyme NEIL3 in replication-dependent repair of interstrand DNA cross-links derived from psoralen and abasic sites

Transcriptional consequences of XPA disruption in human cell lines

Xpf suppresses the mutagenic consequences of phagocytosis in Dictyostelium

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