Exposure of Arabidopsis thaliana Mutants to Genotoxic Stress Provides New Insights for the Involvement of TDP1α and TDP1β genes in DNA‐Damage Response.

Genotoxic stress activates the DNA‐damage response (DDR) signalling cascades responsible for maintaining genome integrity. Downstream DNA repair pathways include the tyrosyl‐DNA phosphodiesterase 1 (TDP1) enzyme that hydrolyses the phosphodiester bond between the tyrosine of topoisomerase I (TopI) and 3′‐phosphate of DNA. The plant TDP1 subfamily contains the canonical TDP1α gene and the TDP1β gene whose functions are not fully elucidated. The current study proposes to investigate the involvement of TDP1 genes in DDR‐related processes by using Arabidopsis thaliana mutants treated with genotoxic agents. The phenotypic and molecular characterization of tdp1α, tdp1β and tdp1α/β mutants treated with cisplatin (CIS), curcumin (CUR), NSC120686 (NSC), zeocin (ZEO), and camptothecin (CPT), evidenced that while tdp1β was highly sensitive to CIS and CPT, tdp1α was more sensitive to NSC. Gene expression analyses showing upregulation of the TDP2 gene in the double mutant indicate the presence of compensatory mechanisms. The downregulation of POL2A gene in the tdp1β mutant along with the upregulation of the TDP1β gene in pol2a mutants, together with its sensitivity to replication inhibitors (CIS, CTP), point towards a function of this gene in the response to replication stress. Therefore, this study brings novel information relative to the activity of TDP1 genes in plants. Summary Statement: The function of the plant TDP1 genes and their roles in DDR are far from being elucidated. By using Arabidopsis thaliana single and double mutants, our study indicates that TDP1β may play relevant functions related to the presence of double‐strand breaks and replication stress, thus providing novel data regarding its role in DNA repair. [ABSTRACT FROM AUTHOR]