DNA damage-induced cell cycle checkpoints and DNA strand break repair in development and tumorigenesis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1999-12

AUTHORS

Gopal K Dasika, Suh-Chin J Lin, Song Zhao, Patrick Sung, Alan Tomkinson, Eva Y-H P Lee

ABSTRACT

Several newly identified tumor suppressor genes including ATM, NBS1, BRCA1 and BRCA2 are involved in DNA double-strand break repair (DSBR) and DNA damage-induced checkpoint activation. Many of the gene products involved in checkpoint control and DSBR have been studied in great detail in yeast. In addition to evolutionarily conserved proteins such as Chk1 and Chk2, studies in mammalian cells have identified novel proteins such as p53 in executing checkpoint control. DSBR proteins including Mre11, Rad50, Rad51, Rad54, and Ku are present in yeast and in mammals. Many of the tumor suppressor gene products interact with these repair proteins as well as checkpoint regulators, thus providing a biochemical explanation for the pleiotropic phenotypes of mutant cells. This review focuses on the proteins mediating G1/S, S, and G2/M checkpoint control in mammalian cells. In addition, mammalian DSBR proteins and their activities are discussed. An intricate network among DNA damage signal transducers, cell cycle regulators and the DSBR pathways is illustrated. Mouse knockout models for genes involved in these processes have provided valuable insights into their function, establishing genomic instability as a major contributing factor in tumorigenesis. More... »

PAGES

1203283

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/sj.onc.1203283

    DOI

    http://dx.doi.org/10.1038/sj.onc.1203283

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1035749732

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/10630641


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