Modulation of MutS ATP-dependent Functional Activities by DNA containing a Cisplatin Compound Lesion (Base Damage and Mismatch)

Sedletska, Yuliya; Fourrier, Laurence; Malinge, Jean-Marc

doi:10.1016/j.jmb.2007.02.048

Cited by 21 publications

(29 citation statements)

References 51 publications

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“…These cisPt crosslinks create severe local DNA lesions that are sensed by cellular proteins, inducing repair, replication bypass or triggering apoptosis [96]. Several protein families can recognise cisPt–DNA adducts, including nucleotide excision repair (NER) proteins [97], homology-directed repair proteins (HDR) [98], mismatch repair (MMR) proteins [99] and non-histone chromosomal high mobility group proteins 1 and 2 (HMG1 and HMG2) [100]. The intrastrand cisPt structural alteration stalls RNA polymerase II.…”

Section: Compoundsmentioning

confidence: 99%

“…The second DNA repair system predominantly involved in coping with cisPt–DNA adducts is error-free HDR, which removes DNA DSBs remaining after cisPt adduct removal [98]. In contrast to the previously mentioned repair pathways that increase cell viability, MMR proteins have been shown to be essential for cisPt-mediated cytotoxicity [99]. cisPt is reported to enhance interactions between MMR proteins MLH1/PMS2 (MutL homolog 1/PMS1 homolog 2, MMR component) and p73, triggering apoptosis [102].…”

Section: Compoundsmentioning

confidence: 99%

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Common Chemical Inductors of Replication Stress: Focus on Cell‐Based Studies

et al. 2017

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DNA replication is a highly demanding process regarding the energy and material supply and must be precisely regulated, involving multiple cellular feedbacks. The slowing down or stalling of DNA synthesis and/or replication forks is referred to as replication stress (RS). Owing to the complexity and requirements of replication, a plethora of factors may interfere and challenge the genome stability, cell survival or affect the whole organism. This review outlines chemical compounds that are known inducers of RS and commonly used in laboratory research. These compounds act on replication by direct interaction with DNA causing DNA crosslinks and bulky lesions (cisplatin), chemical interference with the metabolism of deoxyribonucleotide triphosphates (hydroxyurea), direct inhibition of the activity of replicative DNA polymerases (aphidicolin) and interference with enzymes dealing with topological DNA stress (camptothecin, etoposide). As a variety of mechanisms can induce RS, the responses of mammalian cells also vary. Here, we review the activity and mechanism of action of these compounds based on recent knowledge, accompanied by examples of induced phenotypes, cellular readouts and commonly used doses.

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Section: Compoundsmentioning

confidence: 99%

Section: Compoundsmentioning

confidence: 99%

Common Chemical Inductors of Replication Stress: Focus on Cell‐Based Studies

et al. 2017

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Section: B Chemical Lesionsmentioning

confidence: 99%

“…For example, the ATP-dependent biochemical properties of Escherichia coli MutSα differs when the protein interacts with a DNA oligonucleotide containing a GT mismatch versus a more complex lesion [108]. MutS exhibits substantial affinity for cisplatin 1,2-d[GpG] intrastrand cross-link with a mispaired thymine opposite the 3′ platinated guanine, whether or not it binds ATP [108]. Similar to the effects of CAG hairpin binding on MSH2/MSH3 function [27], Pt binding inhibits MutSα ATPase activity to a rate equivalent to that induced by nonspecific homoduplex DNA [108].…”

Section: B Chemical Lesionsmentioning

confidence: 99%

“…MutS exhibits substantial affinity for cisplatin 1,2-d[GpG] intrastrand cross-link with a mispaired thymine opposite the 3′ platinated guanine, whether or not it binds ATP [108]. Similar to the effects of CAG hairpin binding on MSH2/MSH3 function [27], Pt binding inhibits MutSα ATPase activity to a rate equivalent to that induced by nonspecific homoduplex DNA [108]. Loss or mutations of MSH2, MSH3, and MSH6 typically result in a 2-to 4-fold increase in lesion tolerance [109], which contributes significantly to the failure of cancer therapy [109,110].…”

Section: B Chemical Lesionsmentioning

confidence: 99%

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Hijacking of the mismatch repair system to cause CAG expansion and cell death in neurodegenerative disease

McMurray

2008

DNA Repair

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Mammalian cells have evolved sophisticated DNA repair systems to correct mispaired or damaged bases and extrahelical loops. Emerging evidence suggests that, in some cases, the normal DNA repair machinery is "highjacked" to become a causative factor in mutation and disease, rather than act as a safeguard of genomic integrity. In this review, we consider two cases in which active MMR leads to mutation or to cell death. There may be similar mechanisms by which uncoupling of normal MMR recognition from downstream repair allows triplet expansions underlying human neurodegenerative disease, or cell death in response to chemical lesion.

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FEN1 promotes tumor progression and confers cisplatin resistance in non-small-cell lung cancer

Luo

Zhu

et al. 2017

Mol Oncol

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Lung cancer is one of the leading causes of cancer mortality worldwide. The therapeutic effect of chemotherapy is limited due to the resistance of cancer cells, which remains a challenge in cancer therapeutics. In this work, we found that flap endonuclease 1 (FEN1) is overexpressed in lung cancer cells. FEN1 is a major component of the base excision repair pathway for DNA repair systems and plays important roles in maintaining genomic stability through DNA replication and repair. We showed that FEN1 is critical for the rapid proliferation of lung cancer cells. Suppression of FEN1 resulted in decreased DNA replication and accumulation of DNA damage, which subsequently induced apoptosis. Manipulating the amount of FEN1 altered the response of lung cancer cells to chemotherapeutic drugs. A small‐molecule inhibitor (C20) was used to target FEN1 and this enhanced the therapeutic effect of cisplatin. The FEN1 inhibitor significantly suppressed cell proliferation and induced DNA damage in lung cancer cells. In mouse models, the FEN1 inhibitor sensitized lung cancer cells to a DNA damage‐inducing agent and efficiently suppressed cancer progression in combination with cisplatin treatment. Our study suggests that targeting FEN1 may be a novel and efficient strategy for a tumor‐targeting therapy for lung cancer.

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Modulation of MutS ATP-dependent Functional Activities by DNA containing a Cisplatin Compound Lesion (Base Damage and Mismatch)

Cited by 21 publications

References 51 publications

Common Chemical Inductors of Replication Stress: Focus on Cell‐Based Studies

Common Chemical Inductors of Replication Stress: Focus on Cell‐Based Studies

Hijacking of the mismatch repair system to cause CAG expansion and cell death in neurodegenerative disease

FEN1 promotes tumor progression and confers cisplatin resistance in non-small-cell lung cancer

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