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Involvement of global genome repair, transcription coupled repair, and chromatin remodeling in UV DNA damage response changes during development.

Lans H, Marteijn JA, Schumacher B, Hoeijmakers JH, Jansen G, Vermeulen W - PLoS Genet. (2010)

Bottom Line: Currently, it is not well understood to what extent both pathways contribute to genome maintenance and cell survival in a developing organism exposed to UV light.Here, we show that eukaryotic NER, initiated by two distinct subpathways, is well conserved in the nematode Caenorhabditis elegans.In germ cells and early embryos, we find that GGR is the major pathway contributing to normal development and survival after UV irradiation, whereas in later developmental stages TCR is predominantly engaged.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Medical Genetics Center, Erasmus MC, Rotterdam, The Netherlands.

ABSTRACT
Nucleotide Excision Repair (NER), which removes a variety of helix-distorting lesions from DNA, is initiated by two distinct DNA damage-sensing mechanisms. Transcription Coupled Repair (TCR) removes damage from the active strand of transcribed genes and depends on the SWI/SNF family protein CSB. Global Genome Repair (GGR) removes damage present elsewhere in the genome and depends on damage recognition by the XPC/RAD23/Centrin2 complex. Currently, it is not well understood to what extent both pathways contribute to genome maintenance and cell survival in a developing organism exposed to UV light. Here, we show that eukaryotic NER, initiated by two distinct subpathways, is well conserved in the nematode Caenorhabditis elegans. In C. elegans, involvement of TCR and GGR in the UV-induced DNA damage response changes during development. In germ cells and early embryos, we find that GGR is the major pathway contributing to normal development and survival after UV irradiation, whereas in later developmental stages TCR is predominantly engaged. Furthermore, we identify four ISWI/Cohesin and four SWI/SNF family chromatin remodeling factors that are implicated in the UV damage response in a developmental stage dependent manner. These in vivo studies strongly suggest that involvement of different repair pathways and chromatin remodeling proteins in UV-induced DNA repair depends on developmental stage of cells.

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Related in: MedlinePlus

L1 larvae and egg survival following UV irradiation.The percentages (survival) of animals that developed beyond the L2 larval stage following UV irradiation are plotted against the indicated UVB-doses of L1 larvae (A–D) or eggs (F, G). (A, B) shows the survival of animals carrying mutations in general NER factors, (C) shows the survival of rad-23 and csb-1 single and double mutants, (D) shows the survival of xpc-1 single and double mutants. (E) shows a simplified model of GGR and TCR in L1 larvae. In (F, G), eggs of wild type, rad-23 and csb-1 mutants were irradiated (20 and 40 J/m2, respectively) 1, 4 or 8 hours after collection using hypochlorite. In (A–D), each line represents the mean of two or more independent experiments, each performed in duplicate (typically, n>80). (F, G) show the mean of a representative experiment performed in duplicate (n>50 eggs). Significant differences (p<0.05) compared to wild type are indicated by an asterisk. Error bars denote the s.e.m.
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pgen-1000941-g005: L1 larvae and egg survival following UV irradiation.The percentages (survival) of animals that developed beyond the L2 larval stage following UV irradiation are plotted against the indicated UVB-doses of L1 larvae (A–D) or eggs (F, G). (A, B) shows the survival of animals carrying mutations in general NER factors, (C) shows the survival of rad-23 and csb-1 single and double mutants, (D) shows the survival of xpc-1 single and double mutants. (E) shows a simplified model of GGR and TCR in L1 larvae. In (F, G), eggs of wild type, rad-23 and csb-1 mutants were irradiated (20 and 40 J/m2, respectively) 1, 4 or 8 hours after collection using hypochlorite. In (A–D), each line represents the mean of two or more independent experiments, each performed in duplicate (typically, n>80). (F, G) show the mean of a representative experiment performed in duplicate (n>50 eggs). Significant differences (p<0.05) compared to wild type are indicated by an asterisk. Error bars denote the s.e.m.

Mentions: Summarized results of Figure 2, Figure 5, Figure 6, and Figure 7. For each gene UV sensitivity in the germ cell and embryo or in the L1 larvae assays is show. + denotes UV hypersensitive, − denotes not UV hypersensitive, compared to wild type.


Involvement of global genome repair, transcription coupled repair, and chromatin remodeling in UV DNA damage response changes during development.

Lans H, Marteijn JA, Schumacher B, Hoeijmakers JH, Jansen G, Vermeulen W - PLoS Genet. (2010)

L1 larvae and egg survival following UV irradiation.The percentages (survival) of animals that developed beyond the L2 larval stage following UV irradiation are plotted against the indicated UVB-doses of L1 larvae (A–D) or eggs (F, G). (A, B) shows the survival of animals carrying mutations in general NER factors, (C) shows the survival of rad-23 and csb-1 single and double mutants, (D) shows the survival of xpc-1 single and double mutants. (E) shows a simplified model of GGR and TCR in L1 larvae. In (F, G), eggs of wild type, rad-23 and csb-1 mutants were irradiated (20 and 40 J/m2, respectively) 1, 4 or 8 hours after collection using hypochlorite. In (A–D), each line represents the mean of two or more independent experiments, each performed in duplicate (typically, n>80). (F, G) show the mean of a representative experiment performed in duplicate (n>50 eggs). Significant differences (p<0.05) compared to wild type are indicated by an asterisk. Error bars denote the s.e.m.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2865526&req=5

pgen-1000941-g005: L1 larvae and egg survival following UV irradiation.The percentages (survival) of animals that developed beyond the L2 larval stage following UV irradiation are plotted against the indicated UVB-doses of L1 larvae (A–D) or eggs (F, G). (A, B) shows the survival of animals carrying mutations in general NER factors, (C) shows the survival of rad-23 and csb-1 single and double mutants, (D) shows the survival of xpc-1 single and double mutants. (E) shows a simplified model of GGR and TCR in L1 larvae. In (F, G), eggs of wild type, rad-23 and csb-1 mutants were irradiated (20 and 40 J/m2, respectively) 1, 4 or 8 hours after collection using hypochlorite. In (A–D), each line represents the mean of two or more independent experiments, each performed in duplicate (typically, n>80). (F, G) show the mean of a representative experiment performed in duplicate (n>50 eggs). Significant differences (p<0.05) compared to wild type are indicated by an asterisk. Error bars denote the s.e.m.
Mentions: Summarized results of Figure 2, Figure 5, Figure 6, and Figure 7. For each gene UV sensitivity in the germ cell and embryo or in the L1 larvae assays is show. + denotes UV hypersensitive, − denotes not UV hypersensitive, compared to wild type.

Bottom Line: Currently, it is not well understood to what extent both pathways contribute to genome maintenance and cell survival in a developing organism exposed to UV light.Here, we show that eukaryotic NER, initiated by two distinct subpathways, is well conserved in the nematode Caenorhabditis elegans.In germ cells and early embryos, we find that GGR is the major pathway contributing to normal development and survival after UV irradiation, whereas in later developmental stages TCR is predominantly engaged.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Medical Genetics Center, Erasmus MC, Rotterdam, The Netherlands.

ABSTRACT
Nucleotide Excision Repair (NER), which removes a variety of helix-distorting lesions from DNA, is initiated by two distinct DNA damage-sensing mechanisms. Transcription Coupled Repair (TCR) removes damage from the active strand of transcribed genes and depends on the SWI/SNF family protein CSB. Global Genome Repair (GGR) removes damage present elsewhere in the genome and depends on damage recognition by the XPC/RAD23/Centrin2 complex. Currently, it is not well understood to what extent both pathways contribute to genome maintenance and cell survival in a developing organism exposed to UV light. Here, we show that eukaryotic NER, initiated by two distinct subpathways, is well conserved in the nematode Caenorhabditis elegans. In C. elegans, involvement of TCR and GGR in the UV-induced DNA damage response changes during development. In germ cells and early embryos, we find that GGR is the major pathway contributing to normal development and survival after UV irradiation, whereas in later developmental stages TCR is predominantly engaged. Furthermore, we identify four ISWI/Cohesin and four SWI/SNF family chromatin remodeling factors that are implicated in the UV damage response in a developmental stage dependent manner. These in vivo studies strongly suggest that involvement of different repair pathways and chromatin remodeling proteins in UV-induced DNA repair depends on developmental stage of cells.

Show MeSH
Related in: MedlinePlus