News & views FANC proteins). This is consistent with genetic Research, University of Copenhagen, DK-2200 Patel, K. J. Nature 475, 53–58 (2011). evidence that FANC proteins are required in Copenhagen, Denmark. 6. Chang, J. S., Hsiao, J.-R. & Chen, C.-H. J. Biomed. Sci. 24, 19 (2017). the two-tier system that protects against e-mail: [email protected] 7. Hira, A. et al. Blood 122, 3206–3209 (2013) acetaldehyde damage. However, the authors 8. Walter, J., Sun, L. & Newport, J. Mol. Cell 1, 519–529 1. Wang, M. et al. Chem. Res. Toxicol. 13, 1149–1157 (2000). unexpectedly discovered that about half of the (1998). 2. Hodskinson, M. R. et al. Nature 579, 603–608 (2020). 9. Räschle, M. et al. Cell 134, 969–980 (2008). crosslinks are fixed by a second, faster mecha- 3. Fiesco-Roa, M. O., Giri, N., McReynolds, L. J., Best, A. F. & 10. Knipscheer, P. et al. Science 326, 1698–1701 (2009). nism. Further investigation revealed that this Alter, B. P. Blood Rev. 37, 100589 (2019). 11. Semlow, D. R., Zhang, J., Budzowska, M., Drohat, A. C. & 4. Sasaki, M. S. & Tonomura, A. Cancer Res. 33, 1829–1836 Walter, J. C. Cell 167, 498–511 (2016). second route also involves DNA replication, (1973). but is independent of the FA pathway. 5. Langevin, F., Crossan, G. P., Rosado, I. V., Arends, M. J. & This article was published online on 4 March 2020. Surprisingly, in the fast repair route, no cuts are made to the DNA strands; instead, the ICL is Atmospheric science probably cut within the crosslink. This mode of repair results in the reversion of the crosslink to an undamaged base on one of the DNA strands, but leaves an adduct on the other Jet stream stops shifting strand (Fig. 1), which specialized DNA-repli- cation enzymes can bypass to complete repair. as ozone layer recovers This mechanism is reminiscent of the one that 11 fixes ICLs generated by the drug psoralen , Alexey Yu. Karpechko but involves different enzymes. By avoid- ing DNA breaks — which are associated with The Antarctic ozone hole shifted the jet stream in the genomic rearrangements, one of the hallmarks Southern Hemisphere poleward, leading to hemisphere-wide of cancer and ageing — the fast repair mech- climatic changes. But the Montreal Protocol, which banned anism has an important advantage over the FA pathway. Taken together, Hodskinson and ozone-depleting substances, has halted the shift. See p.544 colleagues’ findings provide a holistic glimpse of how acetaldehyde-derived crosslinks are cleared from DNA, and support the idea that The discovery1 of a hole in the springtime lowest layer of the atmosphere). these lesions contribute to FA. atmospheric ozone layer over the Antarctic It is not obvious why changes to strato- The authors do not identify a protein that in the mid-1980s revealed the threat posed spheric winds affect circulation in the cleaves the crosslinks in the newly described by human-made ozone-depleting sub- under lying troposphere. The stratosphere repair route. One can therefore only speculate stances (ODSs): the damage caused by these represents only about 15% of the atmospheric as to whether cleavage occurs spontaneously compounds exposes people and Earth’s eco- mass, and therefore, when in motion, has as a consequence of mechanical forces gener- systems to harmful ultraviolet radiation. A much less momentum than the troposphere. ated during replication as the DNA unwinds, or related, unexpected effect was revealed in Yet observations and computational model- is the result of enzymatic activity. If it is indeed the early 2000s, when studies2,3 showed that ling confirm that the tropospheric jet stream an enzymatic process, identifying the compo- the Antarctic ozone hole, which resides at alti- is sensitive to changes in stratospheric winds nents of the pathway will be a challenge, but tudes of around 10–20 kilometres, has affected at monthly, seasonal and decadal timescales, could open up opportunities for therapies: atmospheric circulation all the way down to and that the cooling of the polar stratosphere stimulation of the pathway might alleviate the the surface in the Southern Hemisphere — is associated with a poleward shift of the symptoms of FA, or reduce the incidence of most notably, by shifting the summertime tropospheric jet stream7. alcohol-derived cancers. jet stream poleward. The production and use By the end of the twentieth century, the The identification of the protein(s) involved of ODSs was banned by the Montreal Proto- summer time tropospheric jet stream had in the crosslink cleavage would also allow col of 1987 and its subsequent amendments. shifted by about 2° of latitude, altering the in vivo experiments to test whether impair- Atmospheric ODS concentrations are there- transport of atmospheric heat and moisture. ment of the alternative repair route increases fore decreasing, and the first signs of ozone- This contributed to warming of the Antarctic acetaldehyde toxicity, especially under condi- layer recovery have emerged4,5. On page 544, Peninsula, Patagonia and New Zealand, and to tions in which this molecule is not detoxified Banerjee et al.6 report that the hole-associated drying of western Tasmania and western New by metabolism. Furthermore, mutations in the circulation effects have paused since ozone Zealand, and affected the circulation, temper- genes encoding proteins involved in this path- recovery started. ature and salinity of the Southern Ocean8,9. way might reveal the existence of a new group Stratospheric ozone absorbs ultraviolet A cessation of the tropospheric-circulation of people who have an FA-like disorder. In the solar radiation, and the absorbed energy trends since the beginning of the twenty-first meantime, Hodskinson and colleagues’ study heats the stratosphere, the atmosphere’s century has previously been noted10, but underlines the need to develop better assays second-lowest layer. Consequently, ozone Banerjee and colleagues are the first to for- to study ICLs and other types of DNA damage depletion and the related lack of heating mally attribute it to the effects of the Montreal in cells. By studying the repair of specific DNA cool the stratosphere — indeed, the Antarc- Protocol. lesions induced by compounds such as acet- tic springtime stratosphere cooled by about The authors had to overcome several aldehyde, or other mutagens that arise in the 7 °C between the late 1960s and late 1990s difficulties to demonstrate that the poleward body, we are likely to uncover other cellular as a result of the ozone hole2. This cooling shift has paused, and to attribute the pause defence mechanisms against cytotoxic DNA increased the north–south temperature to changes in stratospheric ozone levels. damage. gradient between the southern mid-latitudes First, the natural year-to-year variability of and the Antarctic, which strengthened the atmospheric circulation in the mid- and polar Irene Gallina and Julien P. Duxin are in the stratospheric westerly winds in the Southern latitudes is large, which makes it challenging Faculty of Health and Medical Sciences, Hemisphere and, in turn, caused a poleward to detect atmospheric-circulation trends in Novo Nordisk Foundation Center for Protein shift of the jet stream in the troposphere (the those regions11. Therefore, even though no 500 | Nature | Vol 579 | 26 March 2020 ©2020 Spri nger Nature Li mited. All ri ghts reserved. ©2020 Spri nger Nature Li mited. All ri ghts reserved. recovery exerted a strong enough force on a b 47 the tropospheric circulation to overcome the opposing effect of greenhouse-gas increases. 49° S This is a crucial contribution to the long-stand- ing debate about the relative role of these two 49 51° S Jet factors in past and future circulation trends12. stream ) ° S There is, however, no guarantee that the effects of ozone will dominate these trends in 51 the future. As ozone levels continue to recover, their rate of change and the associated influ- Jet position ( ence on climate will weaken, increasing the relative role of greenhouse-gas increases, 53 especially in ‘business-as-usual’ scenarios in which nothing is done to abate future greenhouse-gas emissions. Such emissions 55 increases might therefore dominate future 1980 1985 1990 1995 2000 2005 2010 2015 tropospheric-circulation changes, and push the jet stream back towards the pole. Figure 1 | Changes in the summertime jet stream in the Southern Hemisphere. a, The jet stream in the Second, the findings add to the evidence Southern Hemisphere forms a near-circle around Antarctica in the troposphere — the lowest layer of the that stratospheric changes can affect the cli- atmosphere. b, Banerjee et al.6 have reanalysed data that record the position of the summertime jet stream mate in the troposphere. This is important during the past few decades. The grey line shows the average position determined from their analysis; the because, despite decades of research, the envelope around the line indicates the minimum to maximum range. The blue line indicates the underlying exact mechanism of stratosphere–tropo- trend, and shows that the jet stream shifted from about 49° S to 51° S between 1980 and 2000 — the years when sphere coupling is poorly understood7. The the stratospheric ozone layer over Antarctica was becoming depleted. The trend alters after 2000, when the lack of understanding does not compromise ozone layer began to recover as a result of the Montreal Protocol, which banned ozone-depleting substances; Banerjee and colleagues’ results, but more the position of the jet stream did not alter significantly during this period. Banerjee and colleagues show that research is needed to increase confidence in ozone recovery is the cause of the pause in the jet-stream shift. (Graph from Fig. 1b of ref. 6.) future climate-change projections. Finally, the authors’ results provide a clear statistically significant poleward shift has concentrations, by contrast, pushed the signal that human actions can affect Earth’s been observed since 2000 (as Banerjee and tropospheric jet poleward during both climate: the Montreal Protocol has paused co-authors report; Fig.