Nucleotide excision repair- and p53-deficient mouse models in cancer research

Hoogervorst, Esther M.; Steeg, Harry van; Vries, Annemieke de

doi:10.1016/j.mrfmmm.2005.01.018

Cited by 25 publications

(16 citation statements)

References 146 publications

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“…Since ionizing radiation and certain chemotherapeutic agents induce lethal effects in cancer cells through DNA damage-initiated apoptosis, treatment effect is determined not only by the severity of therapy-induced DNA damage, but also by the capability of tumor cells to repair the damaged DNA and to initiate apoptosis [5,6]. Thus, the cellular functions of DNA repair and programmed cell death are believed to play an important role in controlling the fate of tumor cells in response to chemotherapy or radiation.…”

Section: Introductionmentioning

confidence: 99%

Genetic polymorphisms and treatment response in advanced non-small cell lung cancer

Liu

et al. 2007

Lung Cancer

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Section: Introductionmentioning

confidence: 99%

Genetic polymorphisms and treatment response in advanced non-small cell lung cancer

Liu

et al. 2007

Lung Cancer

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“…PCNA encircles double-stranded DNA as a trimer, forming a sliding clamp that tethers proteins such as polymerases to DNA (5). PCNA is essential not only for DNA replication but also for several forms of DNA repair, including nucleotide excision repair (NER), the major pathway by which cells remove DNA damage introduced by UV light and a variety of chemical carcinogens (10). After recognition of the lesion, the damaged strand is excised and resynthesized in a process requiring PCNA.…”

mentioning

confidence: 99%

Nuclear Dynamics of PCNA in DNA Replication and Repair

Essers

Theil²,

Baldeyron³

et al. 2005

Molecular and Cellular Biology

375

271

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The DNA polymerase processivity factor proliferating cell nuclear antigen (PCNA) is central to both DNA replication and repair. The ring-shaped homotrimeric PCNA encircles and slides along double-stranded DNA, acting as a "sliding clamp" that localizes proteins to DNA. We determined the behavior of green fluorescent protein-tagged human PCNA (GFP-hPCNA) in living cells to analyze its different engagements in DNA replication and repair. Photobleaching and tracking of replication foci revealed a dynamic equilibrium between two kinetic pools of PCNA, i.e., bound to replication foci and as a free mobile fraction. To simultaneously monitor PCNA action in DNA replication and repair, we locally inflicted UV-induced DNA damage. A surprisingly longer residence time of PCNA at damaged areas than at replication foci was observed. Using DNA repair mutants, we showed that the initial recruitment of PCNA to damaged sites was dependent on nucleotide excision repair. Local accumulation of PCNA at damaged regions was observed during all cell cycle stages but temporarily disappeared during early S phase. The reappearance of PCNA accumulation in discrete foci at later stages of S phase likely reflects engagements of PCNA in distinct genome maintenance processes dealing with stalled replication forks, such as translesion synthesis (TLS). Using a ubiquitination mutant of GFP-hPCNA that is unable to participate in TLS, we noticed a significantly shorter residence time in damaged areas. Our results show that changes in the position of PCNA result from de novo assembly of freely mobile replication factors in the nucleoplasmic pool and indicate different binding affinities for PCNA in DNA replication and repair.Proper duplication, maintenance, and repair of the genome are essential for ensuring genomic stability. Defects in any of these processes contribute to the onset and progression of cancer (9), because genomic DNA is subject to damage by both environmental agents and endogenous metabolic processes. In addition, stalling of the DNA replication machinery, which occurs upon encountering damaged DNA, is a challenging problem for cells. A variety of DNA damage bypass and repair mechanisms rescue replication after encountering DNA lesions. Protein clamps on DNA have been implicated in all processes of DNA metabolism, including DNA replication and repair. The most extensively investigated protein clamp in eukaryotes is the DNA polymerase processivity factor proliferating cell nuclear antigen (PCNA).PCNA is a central protein in both DNA replication and repair. PCNA encircles double-stranded DNA as a trimer, forming a sliding clamp that tethers proteins such as polymerases to DNA (5). PCNA is essential not only for DNA replication but also for several forms of DNA repair, including nucleotide excision repair (NER), the major pathway by which cells remove DNA damage introduced by UV light and a variety of chemical carcinogens (10). After recognition of the lesion, the damaged strand is excised and resynthesized in a process requiring PCNA. ...

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“…p53 Protein is involved in the regulation of cell cycle and apoptosis, as well as DNA repair, mainly by acting as a transcription factor for cellular key proteins involved in these processes. The significance of p53 protein as a tumour suppressor is demonstrated by studies on p53-deficient mice that develop tumours (predominantly lymphomas) spontaneously by the age of 6 months (reviewed by Hoogervorst et al, 2005). p53 -/-Mice are viable except for some female embryos that die before birth of neural tube defects.…”

Section: Studies On Tp53mentioning

confidence: 99%

Integrating Field Analyses with Laboratory Exposures to Assess Ecosystems Health

Hellou¹,

Beach²,

Leonard³

et al. 2012

Polycyclic Aromatic Compounds

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initiated a programme on the evaluation of the carcinogenic risk of chemicals to humans involving the production of critically evaluated monographs on individual chemicals. The programme was subsequently expanded to include evaluations of carcinogenic risks associated with exposures to complex mixtures, life-style factors and biological and physical agents, as well as those in specific occupations. The objective of the programme is to elaborate and publish in the form of monographs critical reviews of data on carcinogenicity for agents to which humans are known to be exposed and on specific exposure situations; to evaluate these data in terms of human risk with the help of international working groups of experts in chemical carcinogenesis Publications of the World Health Organization enjoy copyright protection in accordance with the provisions of Protocol 2 of the Universal Copyright Convention. All rights reserved.The International Agency for Research on Cancer welcomes requests for permission to reproduce or translate its publications, in part or in full. Requests for permission to reproduce or translate IARC publications -whether for sale or for noncommercial distribution -should be addressed to WHO Press, at the above address (fax: +41 22 791 4806; email: permissions@who.int).The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the World Health Organization concerning the legal status of any country, territory, city, or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.The IARC Monographs Working Group alone is responsible for the views expressed in this publication. IARC Library Cataloguing in Publication Data NOTE TO THE READERThe term 'carcinogenic risk' in the IARC Monographs series is taken to mean that an agent is capable of causing cancer under some circumstances. The Monographs evaluate cancer hazards, despite the historical presence of the word 'risks' in the title.Inclusion of an agent in the Monographs does not imply that it is a carcinogen, only that the published data have been examined. Equally, the fact that an agent has not yet been evaluated in a Monograph does not mean that it is not carcinogenic.The evaluations of carcinogenic risk are made by international working groups of independent scientists and are qualitative in nature. No recommendation is given for regulation or legislation.Anyone who is aware of published data that may alter the evaluation of the carcinogenic risk of an agent to humans is encouraged to make this information available to the Section of IARC Monographs, International Agency for...

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Nucleotide excision repair- and p53-deficient mouse models in cancer research

Cited by 25 publications

References 146 publications

Genetic polymorphisms and treatment response in advanced non-small cell lung cancer

Genetic polymorphisms and treatment response in advanced non-small cell lung cancer

Nuclear Dynamics of PCNA in DNA Replication and Repair

Integrating Field Analyses with Laboratory Exposures to Assess Ecosystems Health

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