Repair of and checkpoint response to topoisomerase I-mediated DNA damage

Pommier, ﻿Yves; Redon, Christophe E.; Rao, V. Ashutosh; Seiler, Jennifer A.; Sordet, Olivier; Takemura, Haruyuki; Antony, Smitha; Meng, Lingjun; Liao, Zhiyong; Kohlhagen, Glenda; Zhang, Hongliang; Kohn, Kurt W.

doi:10.1016/j.mrfmmm.2003.08.016

Cited by 275 publications

(250 citation statements)

References 252 publications

(341 reference statements)

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“…Understanding the transcriptional response to Top1cc is of particular interest as the CPT derivatives irinotecan and topotecan are used to treat human cancers. 18 Moreover, transcriptional responses to Top1cc may occur spontaneously under normal conditions as Top1cc are readily stabilized by endogenous DNA alterations, 15,52,53 which may lead, if not repaired, to neurological diseases such as SCAN1. 54 …”

Section: Discussionmentioning

confidence: 99%

Hyperphosphorylation of RNA Polymerase II in Response to Topoisomerase I Cleavage Complexes and Its Association with Transcription- and BRCA1-dependent Degradation of Topoisomerase I

Sordet

Larochelle

Nicolas

et al. 2008

Journal of Molecular Biology

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SUMMARYThe progression of RNA polymerase II can be blocked by lesions on the DNA template. In this study, we focused in the modifications of the largest subunit of RNA polymerase II, Rpb1, in response to stabilized topoisomerase I (Top1)-DNA cleavage complexes. In addition to DNA modifications (base damages and strand breaks), Top1 cleavage complexes can be trapped by camptothecin and its derivatives used in cancer treatment. We find that, within a few minutes, camptothecin produces the complete hyperphosphorylation of Rpb1 in both primary and transformed cancer cells. Hyperphosphorylation is rapidly reversible following camptothecin removal. Hyperphosphorylation occurs selectively on the serine-5 residue of the conserved heptapeptide repeats in the Rpb1-carboxyterminal domain and is mediated principally by the TFIIH-associated kinase, Cdk7. Hyperphosphorylated Rpb1 is not primarily targeted for proteosomal degradation, but instead is subjected to cycles of phosphorylation and dephosphorylation as long as Top1 cleavage complexes are trapped by camptothecin. Finally, we show that transcription-induced degradation of Top1 is Brca1-dependent, suggesting a role for Brca1 in the repair or removal of transcription-blocking Top1-DNA cleavage complexes.

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Section: Discussionmentioning

confidence: 99%

Hyperphosphorylation of RNA Polymerase II in Response to Topoisomerase I Cleavage Complexes and Its Association with Transcription- and BRCA1-dependent Degradation of Topoisomerase I

Sordet

Larochelle

Nicolas

et al. 2008

Journal of Molecular Biology

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“…In this case, a trapped DNA:topoisomerase 1 (Top1) complex comprises the lesion. Top1 is essential for the relaxation of DNA supercoiling ahead of the replication machinery [53,54]. If Top1 is inhibited either chemically (for example through the action of the chemotherapeutic drug camptothecin) or as a result of clustered ROS damage, the protein remains bound to the DNA creating a toxic single-strand break in actively replicating cells [55].…”

Section: Strand-breaks Generated By Topoisomerase Poisonsmentioning

confidence: 99%

“…After lesion removal by Tdp1, PNKP can then transfer the phosphate group from the 3' to the 5' terminus, thus preparing the DNA ends for repair [58]. If any gapfilling activity is required, pol ß is considered a likely candidate [54,[59][60][61][62]. Interestingly, both PNKP and pol ß are known to interact with XRCC1 and it has recently been reported that Tdp1, critical for the repair of these Top1-mediated lesions, co-immunoprecipitated with XRCC1 [61].…”

Section: Strand-breaks Generated By Topoisomerase Poisonsmentioning

confidence: 99%

A unified view of base excision repair: Lesion-dependent protein complexes regulated by post-translational modification

Almeida¹,

Sobol²

2007

DNA Repair

387

374

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Base excision repair (BER) proteins act upon a significantly broad spectrum of DNA lesions that result from endogenous and exogenous sources. Multiple sub-pathways of BER (short-path or longpatch) and newly designated DNA repair pathways (e.g., SSBR and NIR) that utilize BER proteins complicate any comprehensive understanding of BER and its role in genome maintenance, chemotherapeutic response, neurodegeneration, cancer or aging. Herein, we propose a unified model of BER, comprised of three functional processes: Lesion Recognition/Strand Scission, Gap Tailoring and DNA Synthesis/Ligation, each represented by one or more multiprotein complexes and coordinated via the XRCC1/DNA Ligase III and PARP1 scaffold proteins. BER therefore may be represented by a series of repair complexes that assemble at the site of the DNA lesion and mediates repair in a coordinated fashion involving protein-protein interactions that dictate subsequent steps or sub-pathway choice. Complex formation is influenced by post-translational protein modifications that arise from the cellular state or the DNA damage response, providing an increase in specificity and efficiency to the BER pathway. In this review, we have summarized the reported BER proteinprotein interactions and protein post-translational modifications and discuss the impact on DNA repair capacity and complex formation.

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“…However, a variety of conditions (briefly schematized in Fig. 1B), have been shown to increase the frequency of Top1-DNA cleavage complexes by reducing or inhibiting the rate of the religation reaction (for reviews see [7,8]). For example, Top1 inhibitors, such as camptothecin (CPT) and its clinically used derivatives, as well as several non-CPT Top1 inhibitors including the indenoisoquinolines and the indolocarbazoles, selectively and reversibly bind to the Top1-DNA interface [6,9] and slow the rate of Top1-mediated DNA religation.…”

Section: The Formation Of Irreversible Top1 Cleavage Complexesmentioning

confidence: 99%

Tyrosyl-DNA Phosphodiesterase as a Target for Anticancer Therapy

Dexheimer¹,

Antony²,

Marchand³

et al. 2008

ACAMC

144

203

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Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a recently discovered enzyme that catalyzes the hydrolysis of 3′-phosphotyrosyl bonds. Such linkages form in vivo following the DNA processing activity of topoisomerase I (Top1). For this reason, Tdp1 has been implicated in the repair of irreversible Top1-DNA covalent complexes, which can be generated by either exogenous or endogenous factors. Tdp1 has been regarded as a potential therapeutic co-target of Top1 in that it seemingly counteracts the effects of Top1 inhibitors, such as camptothecin and its clinically used derivatives. Thus, by reducing the repair of Top1-DNA lesions, Tdp1 inhibitors have the potential to augment the anticancer activity of Top1 inhibitors provided there is a presence of genetic abnormalities related to DNA checkpoint and repair pathways. Human Tdp1 can also hydrolyze other 3′-end DNA alterations including 3′-phosphoglycolates and 3′-abasic sites indicating it may function as a general 3′-DNA phosphodiesterase and repair enzyme. The importance of Tdp1 in humans is highlighted by the observation that a recessive mutation in the human TDP1 gene is responsible for the inherited disorder, spinocerebellar ataxia with axonal neuropathy (SCAN1). This review provides a summary of the biochemical and cellular processes performed by Tdp1 as well as the rationale behind the development of Tdp1 inhibitors for anticancer therapy.

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Repair of and checkpoint response to topoisomerase I-mediated DNA damage

Cited by 275 publications

References 252 publications

Hyperphosphorylation of RNA Polymerase II in Response to Topoisomerase I Cleavage Complexes and Its Association with Transcription- and BRCA1-dependent Degradation of Topoisomerase I

Hyperphosphorylation of RNA Polymerase II in Response to Topoisomerase I Cleavage Complexes and Its Association with Transcription- and BRCA1-dependent Degradation of Topoisomerase I

A unified view of base excision repair: Lesion-dependent protein complexes regulated by post-translational modification

Tyrosyl-DNA Phosphodiesterase as a Target for Anticancer Therapy

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