Photodamage repair pathways contribute to the accurate maintenance of the DNA methylome landscape upon UV exposure

Abstract

Plants are exposed to the damaging effect of sunlight that induces DNA photolesions. In order to maintain genome integrity, specific DNA repair pathways are mobilized. Upon removal of UV-induced DNA lesions, the accurate re-establishment of epigenome landscape is expected to be a prominent step of these DNA repair pathways. However, it remains poorly documented whether DNA methylation is accurately maintained at photodamaged sites and how photodamage repair pathways contribute to the maintenance of genome/methylome integrities.Using genome wide approaches, we report that UV-C irradiation leads to asymmetric DNA methylation changes. We identified that the specific DNA repair pathways involved in the repair of UV-induced DNA lesions, Direct Repair (DR) and Global Genome Repair (GGR), prevent the excessive alterations of DNA methylation landscape. Moreover, we identified that UV-C irradiation induced chromocenter reorganization and that photodamage repair factors control this dynamics. The methylome changes rely on misregulation of maintenance, de novo and active DNA demethylation pathways highlighting that molecular processes related to genome and methylome integrities are closely interconnected. Importantly, we identified that photolesions are sources of DNA methylation changes in both, constitutive and facultative heterochromatin. This study unveils that DNA repair factors, together with small RNA, act to accurately maintain both genome and methylome integrities at photodamaged silent genomic regions, strengthening the idea that plants have evolved sophisticated interplays between DNA methylation dynamics and DNA repair. Availability of data and materialsWGBS, DNA-seq and small RNA-seq raw data generated in this work are publicly accessible through the GEO registration number : GSE132750. Authors' contributionsSG and VC performed bioinformatics. PJtoB performed cytogenetics, developed the automated image analysis program with JMu and analyzed the data. SG, VC, PJtoB and JMu wrote the methods section. JM designed experiments, prepared the biological samples, analyzed the data and wrote the manuscript. All authors read and approved the final manuscript.

Non-coding RNA polymerases that silence transposable elements and reprogram gene expression in plants

“…Resulting 21 nt siRNAs are loaded onto AGO1 in the case of photodamage [123] or onto AGO2 in the case of DNA double-strand breaks (Figure 4c) [192]. These siRNA-AGO complexes could facilitate DNA damage recognition [123,192] and prevent excessive alterations of the DNA methylation landscape upon photodamage [193].…”

Formation and Recognition of UV-Induced DNA Damage within Genome Complexity

“…In human, CPDs and 6-4PPs are mostly formed between TT and TC, and with a lower frequency at CT and CC sequences [ 21 ]. In the model plant Arabidopsis thaliana , CPDs are predominantly formed between CT and TC and to a lower extent between TT and CC [ 22 , 23 ]. Given that dipyrimidines frequencies are quite similar between human and Arabidopsis [ 21 , 22 , 23 ], such differences in reactivity cannot be only explained by a strong bias in dinucleotides composition.…”

“…In the model plant Arabidopsis thaliana , CPDs are predominantly formed between CT and TC and to a lower extent between TT and CC [ 22 , 23 ]. Given that dipyrimidines frequencies are quite similar between human and Arabidopsis [ 21 , 22 , 23 ], such differences in reactivity cannot be only explained by a strong bias in dinucleotides composition. Other factors such as sequence context and chromatin structure should also be considered as putative parameters influencing the formation of UV-induced DNA damage.…”

“…In the model plant Arabidopsis thaliana , this hypothesis seems to partially hold true. Indeed, CPD and 6-4PP mapping show significant enrichment in highly compacted heterochromatic regions [ 23 ].…”

“…How far the epigenetic context is involved in this hotspot formation, in humans, remain unclear. Similarly, in arabidopsis, genomic regions exhibiting heterochromatic features (high compaction, high DNA methylation levels) are more prone to form photoproducts, suggesting that particular epigenomic marks may contribute to such accurate reactivity [ 22 , 23 ].…”