Sall Salimata Ousmane, Alioua Abdelmalek, Staerck Sébastien, Graindorge Stéfanie, Pellicioli Michel, Schuler Jacky, Galindo Catherine, Raffy Quentin, Rousseau Marc, Molinier Jean
Institut de biologie moléculaire des plantes du CNRS, 12 rue du Général Zimmer, 67000, Strasbourg, France.
Institut pluridisciplinaire Hubert Curien, Campus de Cronenbourg, 23 rue Loess, BP 28 67037, Strasbourg Cedex, France.
Plant J. 2025 Jan;121(1):e17180. doi: 10.1111/tpj.17180. Epub 2024 Dec 1.
DNA, is assaulted by endogenous and exogenous agents that lead to the formation of damage. In order to maintain genome integrity DNA repair pathways must be efficiently activated to prevent mutations and deleterious chromosomal rearrangements. Conversely, genome rearrangement is also necessary to allow genetic diversity and evolution. The antagonist interaction between maintenance of genome integrity and rearrangements determines genome shape and organization. Therefore, it is of great interest to understand how the whole linear genome structure behaves upon formation and repair of DNA damage. For this, we used long reads sequencing technology to identify and to characterize genomic structural variations (SV) of wild-type Arabidopsis thaliana somatic cells exposed either to UV-B, to UV-C or to protons irradiations. We found that genomic regions located in heterochromatin are more prone to form SVs than those located in euchromatin, highlighting that genome stability differs along the chromosome. This holds true in Arabidopsis plants deficient for the expression of master regulators of the DNA damage response (DDR), ATM (Ataxia-telangiectasia-mutated) and ATR (Ataxia-telangiectasia-mutated and Rad3-related), suggesting that independent and alternative surveillance processes exist to maintain integrity in genic regions. Finally, the analysis of the radiations-induced deleted regions allowed determining that exposure to UV-B, UV-C and protons induced the microhomology-mediated end joining mechanism (MMEJ) and that both ATM and ATR repress this repair pathway.
DNA会受到内源性和外源性因素的攻击,从而导致损伤的形成。为了维持基因组的完整性,必须有效激活DNA修复途径,以防止突变和有害的染色体重排。相反,基因组重排对于实现遗传多样性和进化也是必要的。维持基因组完整性与重排之间的拮抗相互作用决定了基因组的形状和组织。因此,了解整个线性基因组结构在DNA损伤形成和修复时的行为表现极具意义。为此,我们使用长读长测序技术来识别和表征野生型拟南芥体细胞在受到UV-B、UV-C或质子辐射后产生的基因组结构变异(SV)。我们发现,位于异染色质中的基因组区域比位于常染色质中的区域更容易形成SV,这突出表明基因组稳定性在染色体上存在差异。在缺乏DNA损伤反应(DDR)主要调节因子ATM(共济失调毛细血管扩张突变)和ATR(共济失调毛细血管扩张突变和Rad3相关)表达的拟南芥植株中也是如此,这表明存在独立的和替代性的监测过程来维持基因区域的完整性。最后,对辐射诱导的缺失区域的分析表明,暴露于UV-B、UV-C和质子会诱导微同源性介导的末端连接机制(MMEJ),并且ATM和ATR都会抑制这种修复途径。