Biomedical subjects

Anne B Britt

Publications and source records attributed to Anne B Britt.

5 recordsLinked to original sources

PubMed2006

ATR and ATM play both distinct and additive roles in response to ionizing radiation.

The ATR and ATM protein kinases are known to be involved in a wide variety of responses to DNA damage. The Arabidopsis thaliana genome includes both ATR and ATM orthologs, and plants with null alleles of these genes are viable. Arabidopsis atr and atm mutants display hypersensitivity to gamma-irradiation. To further characterize the roles of ATM and ATR in response to ionizing radiation, we performed a short-term global transcription analysis in wild-type and mutant lines. We found that hundreds of genes are upregulated in response to gamma-irradiation, and that the induction of virtually all of these genes is dependent on ATM, but not ATR. The transcript of CYCB1;1 is unique among the cyclin transcripts in being rapidly and powerfully upregulated in response to ionizing radiation, while other G(2)-associated transcripts are suppressed. We found that both ATM and ATR contribute to the induction of a CYCB1;1:GUS fusion by IR, but only ATR is required for the persistence of this response. We propose that this upregulation of CYCB1;1 does not reflect the accumulation of cells in G(2), but instead reflects a still unknown role for this cyclin in DNA damage response.

Arabidopsis↗

PubMed2005

Tissue-specific regulation of cell-cycle responses to DNA damage in Arabidopsis seedlings.

DNA damage-induced cell-cycle "checkpoint" responses reduce the mutagenic effects of this damage. However, the maintenance of genomic stability comes at a price: the slowing of growth and a delay in the development of critical tissues. In mammals, every mutated cell has the potential to become cancerous and therefore lethal. In plants, the risk of lethal cancers is essentially nil and the costs of delays in development are very high. Here, we investigate DNA damage checkpoint responses in meristematic (root and shoot tip) versus strictly somatic (stomatal and endoreduplicating) tissues in plants. We find that the ionizing radiation (IR)-induced cell-cycle responses observed in the root and shoot tip meristems do not apply to more differentiated tissues.

Arabidopsis↗

PubMed2005

Ionizing radiation-dependent gamma-H2AX focus formation requires ataxia telangiectasia mutated and ataxia telangiectasia mutated and Rad3-related.

The histone variant H2AX is rapidly phosphorylated at the sites of DNA double-strand breaks (DSBs). This phosphorylated H2AX (gamma-H2AX) is involved in the retention of repair and signaling factor complexes at sites of DNA damage. The dependency of this phosphorylation on the various PI3K-related protein kinases (in mammals, ataxia telangiectasia mutated and Rad3-related [ATR], ataxia telangiectasia mutated [ATM], and DNA-PKCs) has been a subject of debate; it has been suggested that ATM is required for the induction of foci at DSBs, whereas ATR is involved in the recognition of stalled replication forks. In this study, using Arabidopsis as a model system, we investigated the ATR and ATM dependency of the formation of gamma-H2AX foci in M-phase cells exposed to ionizing radiation (IR). We find that although the majority of these foci are ATM-dependent, approximately 10% of IR-induced gamma-H2AX foci require, instead, functional ATR. This indicates that even in the absence of DNA replication, a distinct subset of IR-induced damage is recognized by ATR. In addition, we find that in plants, gamma-H2AX foci are induced at only one-third the rate observed in yeasts and mammals. This result may partly account for the relatively high radioresistance of plants versus yeast and mammals.

Arabidopsis↗

PubMed2003

Re-engineering plant gene targeting.

The genome sequence of Arabidopsis is complete and the genomes of plants representing legumes (Medicago truncatula) and grasses (rice) will soon follow. The rate at which new genes have been discovered has far outstripped the pace at which their function is determined. The greatest hurdle that plant biologists face in assigning gene function and in crop improvement is the lack of efficient and robust technologies to generate gene replacements or targeted gene knockouts. Many of the factors underlying these events remain to be elucidated. This review addresses the current status of plant gene targeting and what is known about the associated plant DNA repair mechanisms.

DNA, Plant↗

PubMed2003

Ku80- and DNA ligase IV-deficient plants are sensitive to ionizing radiation and defective in T-DNA integration.

Double-strand break (DSB) repair pathways catalyze the rejoining of broken chromosomes and the integration of transforming DNAs. These processes have been well characterized in bacteria, fungi, and animals. Plants are generally thought primarily to utilize a non-homologous end joining (NHEJ) pathway to repair DSBs and integrate transgenes, as transforming DNAs with large tracts of homology to the chromosome are integrated at random. In order to test the hypothesis that NHEJ is an important pathway for the repair of DSBs in plants, we isolated T-DNA insertion mutations in the Arabidopsis homologs of the Ku80 and DNA ligase IV genes, required for the initiation and completion, respectively, of NHEJ. Both mutants were hypersensitive to the cytostatic effects of gamma radiation, suggesting that NHEJ is indeed a critical pathway for the repair of DSBs. T-DNA insertion rates were also decreased in the mutants, indicating that Ku80 and DNA ligase IV play an important role in either the mechanism or the regulation of T-DNA integration in Arabidopsis.

Alleles↗