Defining the function of xeroderma pigmentosum group F protein in psoralen interstrand cross-link-mediated DNA repair and mutagenesis

Chen, Zhiwen; Xu, Xiaoxin; Harrison, Jason K.; Gan, Wang

doi:10.1042/bj20031143

Cited by 10 publications

(14 citation statements)

References 48 publications

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“…These results suggest that the entire NER pathway is not necessary to generate DSB in cells, and that the XPF protein specifically participates in an NER-independent function that is required and probably rate-limiting for DSB formation in human cells. This conclusion is generally in agreement with prior work, which indicated that the NER functions of XPF are distinct from its role in ICL processing [23,47,48]. Our work in human cells corroborates and complements prior work, all in Chinese hamster ovary cells, demonstrating that ERCC1, which normally is in a heterodimeric complex with XPF, is required for the initial incisions and γ-H2AX formation [32], and that XPF and ERCC1 are required for incisions leading to DSB in an in vitro assay [14].…”

Section: Discussionsupporting

confidence: 93%

“…In addition, XP-F (XP2YO-SV) cells stably transfected with a plasmid encoding wildtype XPF cDNA were examined. In contrast to XP-F cells which had nearly undetectable XPF protein, XPF-corrected cells expressed ~40% of the level of XPF found in control GM637 cells, as previously described [23] (Fig. 3B).…”

Section: γ-H2ax Formation Following Psoralen Icl Requires Xpfsupporting

confidence: 85%

“…XP129 cells (from P. Hanawalt) are a partial revertant of XP12RO-SV [19]. XPF-complemented XP-F cells (from G. Wang), were originally established by stably transfecting XPF cDNA into XP2YO-SV [23]. These cells were grown in Dulbecco's modified Eagle medium supplemented with 10% fetal bovine serum at 37 °C.…”

Section: Cellsmentioning

confidence: 99%

“…On the other hand, cells deficient in the XPA protein, which is essential for NER, are defective in ICL removal [17][18][19][20], while XPA and another NER protein, XPC, appear to participate in the recognition of ICL associated with triplex-forming oligonucleotides [21,22]. Additionally, the XPF-ERCC1 heterodimer possesses functions independent of its role as a structure-specific 5′ endonuclease in NER [23]. The XPF-ERCC1 complex possesses an ICL-dependent 3′ to 5′ exonuclease activity in the presence of the RPA protein [24] as well as both 5′ and 3′ endonuclease activities at ICL [25][26][27].…”

Section: Introductionmentioning

confidence: 99%

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γ-H2AX formation in response to interstrand crosslinks requires XPF in human cells

Mogi

2006

DNA Repair

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To further define the molecular mechanisms involved in processing interstrand crosslinks, we monitored the formation of phosphorylated histone H2AX (γ-H2AX), which is generated in chromatin near double strand break sites, following DNA damage in normal and repair-deficient human cells. Following treatment with a psoralen derivative and ultraviolet A radiation doses that produce significant numbers of crosslinks, γ-H2AX levels in nucleotide excision repair-deficient XP-A fibroblasts (XP12RO-SV) increased to levels that were twice those observed in normal control GM637 fibroblasts. A partial XPA revertant cell line (XP129) that is proficient in crosslink removal, exhibited reduced γ-H2AX levels that were intermediate between those of GM637 and XP-A cells. XP-F fibroblasts (XP2YO-SV and XP3YO) that are also repair-deficient exhibited γ-H2AX levels below even control fibroblasts following treatment with psoralen and ultraviolet A radiation. Similarly, another crosslinking agent, mitomycin C, did not induce γ-H2AX in XP-F cells, although it did induce equivalent levels of γ-H2AX in XPA and control GM637 cells. Ectopic expression of XPF in XP-F fibroblasts restored γ-H2AX induction following treatment with crosslinking agents. Angelicin, a furocoumarin which forms only monoadducts and not crosslinks following ultraviolet A radiation, as well as ultraviolet C radiation, resulted only in weak induction of γ-H2AX in all cells, suggesting that the double strand breaks observed with psoralen and ultraviolet A treatment result preferentially following crosslink formation. These results indicate that XPF is required to form γ-H2AX and likely double strand breaks in response to interstrand crosslinks in human cells. Furthermore, XPA may be important to allow psoralen interstrand crosslinks to be processed without forming a double strand break intermediate.

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Section: Discussionsupporting

confidence: 93%

Section: γ-H2ax Formation Following Psoralen Icl Requires Xpfsupporting

confidence: 85%

Section: Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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γ-H2AX formation in response to interstrand crosslinks requires XPF in human cells

Mogi

2006

DNA Repair

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“…In addition, the unique DNA damage generated by cisplatin, ICLs, may also contribute to this ATM activation. Although the mechanism of repairing ICLs is not fully understood, it is known that NER is involved in this repair process (47)(48)(49)(50)(51)(52)(53)(54)(55). It is possible that the ICL-mediated NER process generates the DNA repair intermediates required for ATM activation, whereas the defects of XPA or XPG proteins prevent the NER process and the generation of these DNA repair intermediates.…”

Section: Discussionmentioning

confidence: 99%

The Involvement of Ataxia-telangiectasia Mutated Protein Activation in Nucleotide Excision Repair-facilitated Cell Survival with Cisplatin Treatment

Colton

Wang

et al. 2006

Journal of Biological Chemistry

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DNA damage can lead to either DNA repair with cell survival or to apoptotic cell death. Although the biochemical processes underlying DNA repair and apoptosis have been extensively studied, the mechanisms by which cells determine whether the damage will be repaired or the apoptotic pathway will be activated is largely unknown. We have studied the role of nucleotide excision repair (NER) in cisplatin DNA damage-induced apoptotic cell death using both normal human fibroblasts and NERdefective xeroderma pigmentosum (XP) XPA and XPG cells. It also showed that a functional XPC protein was required for the association of the ATM protein to genomic DNA. These results suggest that the NER process may prevent the cisplatin treatment-induced apoptosis by activating the ATM protein, and that the presence of the XPC protein is essential for recruiting the ATM protein to the DNA template.Many anticancer drugs are targeted to the genomic DNA of cancer cells to generate DNA damage and block DNA replication and/or gene transcription, resulting in cell cycle arrest and apoptotic cell death (apoptosis). However, cancer cells can avoid this DNA damage-induced cell death through several mechanisms. DNA repair is one of the most important mechanisms that prevent DNA damage-induced cell death (1). Although many studies have been done regarding DNA repair and apoptosis (2-7), the molecular mechanism that determines whether the damage will be repaired or that the damaged cells will undergo apoptosis is largely unknown. The lack of such knowledge has significantly limited our understandings of cancer cell drug resistance and hindered our abilities in the design and development of new drugs for effective cancer treatment.Nucleotide excision repair (NER) 2 is the major DNA repair pathway utilized in the repair of bulky DNA damage generated by most environmental insults and therapeutic drugs (1,8,9). The NER process is initiated by DNA damage recognition and the binding of the XPC-HR23B complex to damaged DNA (10 -14), which further recruits other NER components including XPA, TFIIH, XPG, and XPF/ERCC1 to the damaged site (12,13,15,16). The XPG protein makes a 3Ј incision, which is followed by a 5Ј incision made by the XPF/ERCC1, resulting in a singlestranded gap of 27-32 nucleotides (17). The DNA polymerases (pol ⑀ or pol ␦) fill the gap and the DNA ligase seals the gap to complete the DNA repair process. Interestingly, defects in most of the NER proteins, including XPA, XPB, XPD, XPF and XPG, lead to elevated sensitivities of the cells to many DNA damaging reagents. However, defects of XPC and XPE proteins do not cause increased sensitivity of the cells to DNA damaging treatment (18). Therefore, studying the DNA damage-mediated signaling process in these NER-defective cells will provide important insights into the mechanism of DNA repair in preventing DNA damage-induced apoptosis.DNA damage also promotes cell cycle checkpoint regulation. Both ATM and ATR proteins play important roles in DNA damage-induced cell cycle checkpoint regulation...

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Higher expression of XPF is a critical factor in intrinsic chemotherapy resistance of human renal cell carcinoma

Zhang

Shi

Yuan³

et al. 2016

Intl Journal of Cancer

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Human renal cancer is extremely resistant to chemotherapy and radiation therapy. This clinical characteristic reduces the efficacy of chemotherapeutic agents in the treatment of recurrence or metastasis following surgical resection. Understanding the mechanism of chemotherapy resistance in renal cell carcinoma remains a significant challenge. In this study, we have shown that varied level of XPF expression was organ-tissue specific by comparing human renal cancer, bladder cancer, testicular cancer and their normal tissue counterparts, respectively. The expression of XPF was significantly higher in renal cancer than in bladder cancer and testicular cancer and correlated with the clinical characteristic of their chemotherapeutics sensitivity. These novel findings proposed that the intrinsic chemoresistance of human renal cell carcinomas might be derived from the high level of XPF expression. In a panel of five cancer cell lines, decreasing cisplatin sensitivity correlated with increasing levels of XPF expression. Knockdown of XPF expression not only increased sensitivity of renal carcinoma cells to cisplatin treatment by affecting the DNA damage response, including DNA repair, cell cycle regulation and apoptosis, but also increased senescence of renal cancer cell. Furthermore, experiment in vivo confirmed that silenced XPF significantly increased the sensitivity and survival following treatment with cisplatin in xenograft mice bearing renal cell tumor. These findings firstly uncover a partial mechanism of intrinsic chemoresistance in renal cancer and may provide a new approach to break through the obstacle of intrinsic chemoresistance by targeting the XPF protein with a potential new inhibitor.

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Defining the function of xeroderma pigmentosum group F protein in psoralen interstrand cross-link-mediated DNA repair and mutagenesis

Cited by 10 publications

References 48 publications

γ-H2AX formation in response to interstrand crosslinks requires XPF in human cells

γ-H2AX formation in response to interstrand crosslinks requires XPF in human cells

The Involvement of Ataxia-telangiectasia Mutated Protein Activation in Nucleotide Excision Repair-facilitated Cell Survival with Cisplatin Treatment

Higher expression of XPF is a critical factor in intrinsic chemotherapy resistance of human renal cell carcinoma

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