Rad17 homologue of Arabidopsis is involved in the regulation of DNA damage repair and homologous recombination

Rad17 is involved in DNA checkpoint control in yeast and human cells. A homologue of this gene as well as other genes of the pathway (the 9-1-1 complex) are present in Arabidopsis and share conserved sequence domains with their yeast and human counterparts. DNA-damaging agents induce AtRAD17 transcr...

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Veröffentlicht in:The Plant journal : for cell and molecular biology 2004-06, Vol.38 (6), p.954-968
Hauptverfasser: Heitzeberg, F, Chen, I.P, Hartung, F, Orel, N, Angelis, K.J, Puchta, H
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container_issue 6
container_start_page 954
container_title The Plant journal : for cell and molecular biology
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creator Heitzeberg, F
Chen, I.P
Hartung, F
Orel, N
Angelis, K.J
Puchta, H
description Rad17 is involved in DNA checkpoint control in yeast and human cells. A homologue of this gene as well as other genes of the pathway (the 9-1-1 complex) are present in Arabidopsis and share conserved sequence domains with their yeast and human counterparts. DNA-damaging agents induce AtRAD17 transcriptionally. AtRAD17 mutants show increased sensitivity to the DNA-damaging chemicals bleomycin and mitomycin C (MMC), which can be reversed by complementation, suggesting that the loss of function of Rad17 disturbs DNA repair in plant cells. Our results are further confirmed by the phenotype of a mutant of the 9-1-1 complex (Rad9), which is also sensitive to the same chemicals. AtRAD9 and AtRAD17 seem to be epistatic as the double mutant is not more sensitive to the chemicals than the single mutants. The mutants show a delay in the general repair of double-strand breaks (DSBs). However, frequencies of intrachromosomal homologous recombination (HR) are enhanced. Nevertheless, the mutants are proficient for a further induction of HR by genotoxic stresses. Our results indicate that a mutant Rad17 pathway is associated with a general deregulation of DNA repair, which seems to be correlated with a deficiency in non-homologous DSB repair.
doi_str_mv 10.1111/j.1365-313x.2004.02097.x
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A homologue of this gene as well as other genes of the pathway (the 9-1-1 complex) are present in Arabidopsis and share conserved sequence domains with their yeast and human counterparts. DNA-damaging agents induce AtRAD17 transcriptionally. AtRAD17 mutants show increased sensitivity to the DNA-damaging chemicals bleomycin and mitomycin C (MMC), which can be reversed by complementation, suggesting that the loss of function of Rad17 disturbs DNA repair in plant cells. Our results are further confirmed by the phenotype of a mutant of the 9-1-1 complex (Rad9), which is also sensitive to the same chemicals. AtRAD9 and AtRAD17 seem to be epistatic as the double mutant is not more sensitive to the chemicals than the single mutants. The mutants show a delay in the general repair of double-strand breaks (DSBs). However, frequencies of intrachromosomal homologous recombination (HR) are enhanced. Nevertheless, the mutants are proficient for a further induction of HR by genotoxic stresses. Our results indicate that a mutant Rad17 pathway is associated with a general deregulation of DNA repair, which seems to be correlated with a deficiency in non-homologous DSB repair.</description><identifier>ISSN: 0960-7412</identifier><identifier>EISSN: 1365-313X</identifier><identifier>DOI: 10.1111/j.1365-313x.2004.02097.x</identifier><identifier>PMID: 15165187</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Amino Acid Sequence ; amino acid sequences ; Arabidopsis ; Arabidopsis - genetics ; Arabidopsis Proteins ; Arabidopsis RAD17 protein ; Arabidopsis thaliana ; Biological and medical sciences ; Cell Cycle Proteins - chemistry ; Cell Cycle Proteins - isolation &amp; purification ; Cell Cycle Proteins - physiology ; comet assay ; complementary DNA ; DNA damage ; DNA Damage - physiology ; DNA repair ; DNA Repair - physiology ; DNA, Complementary - analysis ; DNA-Binding Proteins ; double‐strand break repair ; Endonucleases - isolation &amp; purification ; exodeoxyribonucleases ; Fundamental and applied biological sciences. Psychology ; genetic complementation ; genetic recombination ; intrachromosomal homologous recombination ; Molecular and cellular biology ; Molecular genetics ; Molecular Sequence Data ; Mutagenesis. 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A homologue of this gene as well as other genes of the pathway (the 9-1-1 complex) are present in Arabidopsis and share conserved sequence domains with their yeast and human counterparts. DNA-damaging agents induce AtRAD17 transcriptionally. AtRAD17 mutants show increased sensitivity to the DNA-damaging chemicals bleomycin and mitomycin C (MMC), which can be reversed by complementation, suggesting that the loss of function of Rad17 disturbs DNA repair in plant cells. Our results are further confirmed by the phenotype of a mutant of the 9-1-1 complex (Rad9), which is also sensitive to the same chemicals. AtRAD9 and AtRAD17 seem to be epistatic as the double mutant is not more sensitive to the chemicals than the single mutants. The mutants show a delay in the general repair of double-strand breaks (DSBs). However, frequencies of intrachromosomal homologous recombination (HR) are enhanced. Nevertheless, the mutants are proficient for a further induction of HR by genotoxic stresses. Our results indicate that a mutant Rad17 pathway is associated with a general deregulation of DNA repair, which seems to be correlated with a deficiency in non-homologous DSB repair.</description><subject>Amino Acid Sequence</subject><subject>amino acid sequences</subject><subject>Arabidopsis</subject><subject>Arabidopsis - genetics</subject><subject>Arabidopsis Proteins</subject><subject>Arabidopsis RAD17 protein</subject><subject>Arabidopsis thaliana</subject><subject>Biological and medical sciences</subject><subject>Cell Cycle Proteins - chemistry</subject><subject>Cell Cycle Proteins - isolation &amp; purification</subject><subject>Cell Cycle Proteins - physiology</subject><subject>comet assay</subject><subject>complementary DNA</subject><subject>DNA damage</subject><subject>DNA Damage - physiology</subject><subject>DNA repair</subject><subject>DNA Repair - physiology</subject><subject>DNA, Complementary - analysis</subject><subject>DNA-Binding Proteins</subject><subject>double‐strand break repair</subject><subject>Endonucleases - isolation &amp; purification</subject><subject>exodeoxyribonucleases</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>genetic complementation</subject><subject>genetic recombination</subject><subject>intrachromosomal homologous recombination</subject><subject>Molecular and cellular biology</subject><subject>Molecular genetics</subject><subject>Molecular Sequence Data</subject><subject>Mutagenesis. Repair</subject><subject>mutagens</subject><subject>mutants</subject><subject>nucleotide sequences</subject><subject>plant proteins</subject><subject>RAD17</subject><subject>RAD9</subject><subject>Recombination, Genetic</subject><subject>Schizosaccharomyces pombe Proteins</subject><subject>sequence analysis</subject><subject>Sequence Homology, Amino Acid</subject><issn>0960-7412</issn><issn>1365-313X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1v1DAQhi1ERZfCX4Bc4JYwjh1_HDisyreqgqCVuFmT2NlmlcRbe1O2_x6nu1W5FcuSR-PnnRnNS0hGoaDpvFsXlIkqZ5TtihKAF1CClsXuCVncf_x-ShagBeSS0_KYPI9xDUAlE_wZOaYVFRVVckHGn2ipzK784Hu_mlzm22wZsO6s38QuZvMdb3x_42wKsu2Vy4JbTT1uOz_O8IfzZWZxwNX8scEuZDja-3p-iinb-KHuxjvFC3LUYh_dy8N7Qi4_fbw4_ZKfff_89XR5ljeVEDJvAECVXHJpnQUOCnip2pqljLXYWuoYV1Bp4Ly2TDqNVDUMBTRco1UtOyFv93U3wV9PLm7N0MXG9T2OLg1lJNWC8Uo_ClKpteZKJFDtwSb4GINrzSZ0A4ZbQ8HMppi1mXdv5t2b2RRzZ4rZJemrQ4-pHpx9EB5cSMCbA4Cxwb4NODZd_IeTUpWCJe79nvvT9e72vwcwFz--zVHSv97rW_QGVyH1uPxVAmUAmnGd1vEXTDmxWQ</recordid><startdate>200406</startdate><enddate>200406</enddate><creator>Heitzeberg, F</creator><creator>Chen, I.P</creator><creator>Hartung, F</creator><creator>Orel, N</creator><creator>Angelis, K.J</creator><creator>Puchta, H</creator><general>Blackwell Science Ltd</general><general>Blackwell Science</general><scope>FBQ</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>200406</creationdate><title>Rad17 homologue of Arabidopsis is involved in the regulation of DNA damage repair and homologous recombination</title><author>Heitzeberg, F ; Chen, I.P ; Hartung, F ; Orel, N ; Angelis, K.J ; Puchta, H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5667-c000824747ded04080428fb3474ddafd1e348059044bd37e9a18c3a60c49ad8f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Amino Acid Sequence</topic><topic>amino acid sequences</topic><topic>Arabidopsis</topic><topic>Arabidopsis - genetics</topic><topic>Arabidopsis Proteins</topic><topic>Arabidopsis RAD17 protein</topic><topic>Arabidopsis thaliana</topic><topic>Biological and medical sciences</topic><topic>Cell Cycle Proteins - chemistry</topic><topic>Cell Cycle Proteins - isolation &amp; purification</topic><topic>Cell Cycle Proteins - physiology</topic><topic>comet assay</topic><topic>complementary DNA</topic><topic>DNA damage</topic><topic>DNA Damage - physiology</topic><topic>DNA repair</topic><topic>DNA Repair - physiology</topic><topic>DNA, Complementary - analysis</topic><topic>DNA-Binding Proteins</topic><topic>double‐strand break repair</topic><topic>Endonucleases - isolation &amp; purification</topic><topic>exodeoxyribonucleases</topic><topic>Fundamental and applied biological sciences. 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A homologue of this gene as well as other genes of the pathway (the 9-1-1 complex) are present in Arabidopsis and share conserved sequence domains with their yeast and human counterparts. DNA-damaging agents induce AtRAD17 transcriptionally. AtRAD17 mutants show increased sensitivity to the DNA-damaging chemicals bleomycin and mitomycin C (MMC), which can be reversed by complementation, suggesting that the loss of function of Rad17 disturbs DNA repair in plant cells. Our results are further confirmed by the phenotype of a mutant of the 9-1-1 complex (Rad9), which is also sensitive to the same chemicals. AtRAD9 and AtRAD17 seem to be epistatic as the double mutant is not more sensitive to the chemicals than the single mutants. The mutants show a delay in the general repair of double-strand breaks (DSBs). However, frequencies of intrachromosomal homologous recombination (HR) are enhanced. Nevertheless, the mutants are proficient for a further induction of HR by genotoxic stresses. Our results indicate that a mutant Rad17 pathway is associated with a general deregulation of DNA repair, which seems to be correlated with a deficiency in non-homologous DSB repair.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>15165187</pmid><doi>10.1111/j.1365-313x.2004.02097.x</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record>
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subjects Amino Acid Sequence
amino acid sequences
Arabidopsis
Arabidopsis - genetics
Arabidopsis Proteins
Arabidopsis RAD17 protein
Arabidopsis thaliana
Biological and medical sciences
Cell Cycle Proteins - chemistry
Cell Cycle Proteins - isolation & purification
Cell Cycle Proteins - physiology
comet assay
complementary DNA
DNA damage
DNA Damage - physiology
DNA repair
DNA Repair - physiology
DNA, Complementary - analysis
DNA-Binding Proteins
double‐strand break repair
Endonucleases - isolation & purification
exodeoxyribonucleases
Fundamental and applied biological sciences. Psychology
genetic complementation
genetic recombination
intrachromosomal homologous recombination
Molecular and cellular biology
Molecular genetics
Molecular Sequence Data
Mutagenesis. Repair
mutagens
mutants
nucleotide sequences
plant proteins
RAD17
RAD9
Recombination, Genetic
Schizosaccharomyces pombe Proteins
sequence analysis
Sequence Homology, Amino Acid
title Rad17 homologue of Arabidopsis is involved in the regulation of DNA damage repair and homologous recombination
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