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Preserving Yeast Genetic Heritage through DNA Damage Checkpoint Regulation and Telomere Maintenance
Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA
Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA 92093, USA
* Author to whom correspondence should be addressed.
Received: 10 September 2012; in revised form: 10 October 2012 / Accepted: 22 October 2012 / Published: 30 October 2012
Abstract: In order to preserve genome integrity, extrinsic or intrinsic DNA damages must be repaired before they accumulate in cells and trigger other mutations and genome rearrangements. Eukaryotic cells are able to respond to different genotoxic stresses as well as to single DNA double strand breaks (DSBs), suggesting highly sensitive and robust mechanisms to detect lesions that trigger a signal transduction cascade which, in turn, controls the DNA damage response (DDR). Furthermore, cells must be able to distinguish natural chromosomal ends from DNA DSBs in order to prevent inappropriate checkpoint activation, DDR and chromosomal rearrangements. Since the original discovery of RAD9, the first DNA damage checkpoint gene identified in Saccharomyces cerevisiae, many genes that have a role in this pathway have been identified, including MRC1, MEC3, RAD24, RAD53, DUN1, MEC1 and TEL1. Extensive studies have established most of the genetic basis of the DNA damage checkpoint and uncovered its different functions in cell cycle regulation, DNA replication and repair, and telomere maintenance. However, major questions concerning the regulation and functions of the DNA damage checkpoint remain to be answered. First, how is the checkpoint activity coupled to DNA replication and repair? Second, how do cells distinguish natural chromosome ends from deleterious DNA DSBs? In this review we will examine primarily studies performed using Saccharomyces cerevisiae as a model system.
Keywords: genome maintenance; DNA damage checkpoint; DNA damage response; double strand breaks (DSB); telomere
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Baldo, V.; Liang, J.; Wang, G.; Zhou, H. Preserving Yeast Genetic Heritage through DNA Damage Checkpoint Regulation and Telomere Maintenance. Biomolecules 2012, 2, 505-523.
Baldo V, Liang J, Wang G, Zhou H. Preserving Yeast Genetic Heritage through DNA Damage Checkpoint Regulation and Telomere Maintenance. Biomolecules. 2012; 2(4):505-523.
Baldo, Veronica; Liang, Jason; Wang, Guoliang; Zhou, Huilin. 2012. "Preserving Yeast Genetic Heritage through DNA Damage Checkpoint Regulation and Telomere Maintenance." Biomolecules 2, no. 4: 505-523.