Repair of DNA interstrand cross-links

Dronkert, Mies L. G.; Kanaar, Roland

doi:10.1016/s0921-8777(01)00092-1

Cited by 530 publications

(572 citation statements)

References 258 publications

Supporting

Mentioning

555

Contrasting

Unclassified

Order By: Relevance

“…Unlike psoralens, mitomycin C forms both monoadducts and ICL in DNA at purine bases in the absence of UV irradiation, and ICL typically constitute a much lower percentage of the total adducts than can be achieved with psoralens and UVA [1,46]. As seen with HMT and UVA treatment, XP-F cells exhibited significantly lower γ-H2AX levels following mityomycin C treatment than GM637 cells (Fig.…”

Section: Mitomycin C Induces γ-H2ax In Gm637 and Xpa But Not Xpf Cellsmentioning

confidence: 82%

“…DNA interstrand crosslinks (ICLs) that covalently link complementary strands of duplex DNA constitute a unique class of DNA damage that strongly inhibits DNA replication and transcription and is highly cytotoxic [1]. Many commonly used chemotherapeutic drugs such as psoralen, mitomycin C, cisplatin and nitrogen mustards generate ICL.…”

Section: Introductionmentioning

confidence: 99%

“…The processing of ICL has been extensively studied in prokaryotes and yeast and appears to involve the nucleotide excision repair (NER) and recombination pathways, as well as lesion bypass and post-replication repair [1,10,11]. Processing of ICL in mammalian cells appears to be mediated by similarly diverse mechanisms as well as transcription [12,13] and certain mismatch repair proteins [14], although the relative importance of differing pathways and the detailed sequence of events remain to be elucidated [1].…”

Section: Introductionmentioning

confidence: 99%

“…Processing of ICL in mammalian cells appears to be mediated by similarly diverse mechanisms as well as transcription [12,13] and certain mismatch repair proteins [14], although the relative importance of differing pathways and the detailed sequence of events remain to be elucidated [1]. For example, the contribution of NER proteins to ICL repair is unclear.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Mogi

2006

DNA Repair

View full text Add to dashboard Cite

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.

show abstract

Section: Mitomycin C Induces γ-H2ax In Gm637 and Xpa But Not Xpf Cellsmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Mogi

2006

DNA Repair

View full text Add to dashboard Cite

show abstract

“…7,26 Impairment of DNA synthesis by ICLs is one of the main reasons for the inhibition of cell proliferation and subsequent cell death when the damage is beyond repair by the cellular machinery. [26][27][28] The cytotoxicity of nitrogen mustard drugs is well correlated with its ability to form ICLs, 26 whereas cisplatin is cytotoxic mainly due to intrastrand crosslinking. 26,28 Thurston et al 29 have demonstrated that the cytotoxicity in several cell lines is directly correlated with ICLs that are induced by therapeutic drugs.…”

Section: Discussionmentioning

confidence: 99%

The novel DNA alkylating agent BO‐1090 suppresses the growth of human oral cavity cancer in xenografted and orthotopic mouse models

Sanjiv

Suman

et al. 2011

Intl Journal of Cancer

View full text Add to dashboard Cite

Oral cancer is the fourth-most common cause of death in males and overall the sixth-most common cause of cancer death in Taiwan. Surgery, radiotherapy and chemotherapy combined with other therapies are the most common treatments for oral cavity cancer. Although cisplatin, 5-fluorouracil and docetaxel are commonly used clinically, there is no drug specific for oral cavity cancer. Here, we demonstrated that derivatives of 3a-aza-cyclopenta[a]indene, a class of newly synthesized alkylating agents, may be drugs more specific for oral cancer based on its potent in vitro cytotoxicity to oral cancer cells and on in vivo xenografts. Among them, BO-1090, bis(hydroxymethyl)-3a-aza-cyclopenta[a]indene derivative, targeted DNA for its cytotoxic effects as shown by inhibition of DNA synthesis (bromodeoxyuridine-based DNA synthesis assay), induction of DNA crosslinking (alkaline gel shift assay), and induction of DNA single-stranded breaks (Comet assay) and double-stranded breaks (c-H2AX focus formation). Following DNA damage, BO-1090 induced G1/S-phase arrest and apoptosis in oral cancer cell lines. The therapeutic potential of BO-1090 was tested in mice that received a xenograft of oral cavity cancer cell lines (SAS or Cal 27 cells). Intravenous injection of BO-1090 significantly suppressed tumor growth in comparison to control mice. BO-1090 also significantly reduced the tumor burden in orthotopic mouse models using SAS cells. There was no significant adverse effect of BO-1090 treatment with this dosage based on whole blood count, biochemical enzyme profiles in plasma and histopathology of various organs in mouse. Taken together, our current results demonstrate that B0-1090 may have potential as a treatment for oral cavity cancer.Oral cavity cancer involving the lesions occurred in the tongue, oropharynx and floor of the mouth is a prevalent type of cancer in developing countries such as India, Pakistan, Bangladesh and Taiwan. 1 In south-central Asia, it is the third-most common cancer, with an average incidence rate of 1 to 10 per 100,000 people. The incidence of oral cancer is also increasing in developed countries. 2 The treatments of oral cancer include surgery, radiation or chemotherapy, depending on the stage and nature of the tumor. 3,4 Unfortunately, only marginal improvement is seen in many patients, and a complete cure is often not achieved. Half of the patients diagnosed with oral cancer succumb to death within 5 years, and for those who survive, the quality of life remains poor. 1 Thus, development of a drug specific for oral cavity cancer is needed so that substantial improvement in treatment can be achieved.The cytotoxic and antitumor properties of alkylating agents are due to their ability to covalently bind to DNA. There are two types of DNA alkylating agents, monofunctional and bifunctional agents. Monofunctional alkylating agents mainly damage DNA by forming methylated adducts, whereas the damage induced by bifunctional alkylating agents includes monoadducts, intrastrand crosslinks and interstrand crossli...

show abstract

Synthesis of Building Blocks and Oligonucleotides with {T}N³‐Alkylene‐N³{T} Cross‐Links

Sun

Noronha

Miller

et al. 2012

CP Nucleic Acid Chemistry

View full text Add to dashboard Cite

This unit describes two methods to directly prepare oligonucleotide duplexes containing an N3thymidine-alkylene-N3thymidine inter-strand cross-link. The inter-strand cross-link can be engineered into the duplex with a number of possible orientations. Both methods require the preparation of a protected thymidine dimer where the N3 atoms of the two nucleosides are covalently attached by an alkyl linker. This linker is prepared starting from a protected diol using two successive alkylation reactions under basic conditions to accomplish the alkylation selectively at the N3 atom of the nucleoside. The chain length of the cross-link can be varied based on the selection of the diol used in the dimer synthesis. The solid-phase mono-phosphoramidite approach involves oligonucleotide synthesis with 3'-O-phosphoramidites, on-column removal of a 3'-O-tert-butyldimethylsilyl protecting group, and continued oligonucleotide synthesis with 5'-O-phosphoramidites. The bis-phosphoramidite approach does not require synthesis with 5'-O-phosphoramidites. At the end of synthesis using either method, the N3thymidine-alkylene-N3thymidine inter-strand cross-linked oligonucleotides can be removed from the solid-support and purified using standard techniques (ion-exchange HPLC) in yields sufficient for various structural studies and repair assays.

show abstract

Repair of DNA interstrand cross-links

Cited by 530 publications

References 258 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 novel DNA alkylating agent BO‐1090 suppresses the growth of human oral cavity cancer in xenografted and orthotopic mouse models

Synthesis of Building Blocks and Oligonucleotides with {T}N³‐Alkylene‐N³{T} Cross‐Links

Contact Info

Product

Resources

About

Repair of DNA interstrand cross-links

Cited by 530 publications

References 258 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 novel DNA alkylating agent BO‐1090 suppresses the growth of human oral cavity cancer in xenografted and orthotopic mouse models

Synthesis of Building Blocks and Oligonucleotides with {T}N3‐Alkylene‐N3{T} Cross‐Links

Contact Info

Product

Resources

About

Synthesis of Building Blocks and Oligonucleotides with {T}N³‐Alkylene‐N³{T} Cross‐Links