AXR1 affects DNA methylation independently of its role in regulating meiotic crossover localization.

Meiotic crossovers (COs) are important for reshuffling genetic information between homologous chromosomes and they are essential for their correct segregation. COs are unevenly distributed along chromosomes and the underlying mechanisms controlling CO localization are not well understood. We previously showed that meiotic COs are mis-localized in the absence of AXR1, an enzyme involved in the neddylation/rubylation protein modification pathway in Arabidopsis thaliana. Here, we report that in axr1-/-, male meiocytes show a strong defect in chromosome pairing whereas the formation of the telomere bouquet is not affected. COs are also redistributed towards subtelomeric chromosomal ends where they frequently form clusters, in contrast to large central regions depleted in recombination. The CO suppressed regions correlate with DNA hypermethylation of transposable elements (TEs) in the CHH context in axr1-/- meiocytes. Through examining somatic methylomes, we found axr1-/- affects DNA methylation in a plant, causing hypermethylation in all sequence contexts (CG, CHG and CHH) in TEs. Impairment of the main pathways involved in DNA methylation is epistatic over axr1-/- for DNA methylation in somatic cells but does not restore regular chromosome segregation during meiosis. Collectively, our findings reveal that the neddylation pathway not only regulates hormonal perception and CO distribution but is also, directly or indirectly, a major limiting pathway of TE DNA methylation in somatic cells.

Ssb2/Nabp1 is dispensable for thymic maturation, male fertility, and DNA repair in mice.

SSB1 and SSB2 are newly identified single-stranded (ss) DNA binding proteins that play a crucial role in genome maintenance in humans. We recently generated a knockout mouse model of Ssb1 and revealed its essential role for neonatal survival. Notably, we found compensatory up-regulation of Ssb2 protein levels in multiple tissues of conditional Ssb1(-/-) mice, suggesting functional compensation between these 2 proteins. We report here the first description of Ssb2(-/-) knockout mice. Surprisingly, unlike Ssb1 knockout mice, Ssb2(-/-) mice are viable and fertile and do not exhibit marked phenotypic changes when compared with their Ssb2(+/+) and Ssb2(+/-) littermates. Notably, we did not detect any pathologic changes in the thymus, spleen, or testes, tissues with the most abundant expression of Ssb2. Moreover, Ssb2(-/-) mouse embryonic fibroblasts (MEFs) did not show any sensitivity to DNA-damaging agents, or defects in DNA repair capacity. However, we observed modest up-regulation of Ssb1 levels in Ssb2(-/-) MEFs as well as in Ssb2(-/-) thymus and spleen, suggesting that Ssb1 is likely able to compensate for the loss of Ssb2 in mice. Altogether, our results show that Ssb2 is dispensable for embryogenesis and adult tissue homeostasis, including thymopoiesis, splenic development, male fertility, and DNA repair in mice.