News & Views | Published:

GENOME INTEGRITY

Resolution of a complex crisis at DNA 3′ termini

Ribonucleotides that are misincorporated into DNA during replication are removed by topoisomerase 1, which generates 3′-terminal adducts that are not amenable to DNA repair and thus compromise genome stability. A recent report by Li et al. reveals that Apn2/APE2 resolves such blocked 3′ termini, thereby suppressing topoisomerase 1–induced mutations at ribonucleotide monophosphate sites within the genome.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    Nick McElhinny, S. A. et al. Nat. Chem. Biol. 6, 774–781 (2010).

  2. 2.

    Williams, J. S., Lujan, S. A. & Kunkel, T. A. Nat. Rev. Mol. Cell Biol. 17, 350–363 (2016).

  3. 3.

    Jinks-Robertson, S. & Klein, H. L. Nat. Struct. Mol. Biol. 22, 176–178 (2015).

  4. 4.

    Kim, N. et al. Science 332, 1561–1564 (2011).

  5. 5.

    Sekiguchi, J. & Shuman, S. Mol. Cell 1, 89–97 (1997).

  6. 6.

    Potenski, C. J., Niu, H., Sung, P. & Klein, H. L. Nature 511, 251–254 (2014).

  7. 7.

    Li, F. et al. Nat. Struct. Mol. Biol. 26, 155–163 (2019).

  8. 8.

    Johnson, R. E. et al. Genes Dev. 12, 3137–3143 (1998).

  9. 9.

    Hadi, M. Z. & Wilson, D. M., III Environ. Mol. Mutagen. 36, 312–324 (2000).

  10. 10.

    Tsuchimoto, D. et al. Nucleic Acids Res. 29, 2349–2360 (2001).

  11. 11.

    Willis, J., Patel, Y., Lentz, B. L. & Yan, S. Proc. Natl Acad. Sci. USA 110, 10592–10597 (2013).

  12. 12.

    Wallace, B. D. et al. Proc. Natl Acad. Sci. USA 114, 304–309 (2017).

  13. 13.

    Burkovics, P., Szukacsov, V., Unk, I. & Haracska, L. Nucleic Acids Res. 34, 2508–2515 (2006).

  14. 14.

    Unk, I., Haracska, L., Johnson, R. E., Prakash, S. & Prakash, L. J. Biol. Chem. 275, 22427–22434 (2000).

  15. 15.

    Unk, I. et al. Mol. Cell. Biol. 22, 6480–6486 (2002).

  16. 16.

    Burkovics, P., Hajdú, I., Szukacsov, V., Unk, I. & Haracska, L. Nucleic Acids Res. 37, 4247–4255 (2009).

  17. 17.

    Lin, Y. et al. Nucleic Acids Res. 46, 2479–2494 (2018).

  18. 18.

    Hossain, M. A., Lin, Y. & Yan, S. Int. J. Mol. Sci. 19, 2389 (2018).

  19. 19.

    Mengwasser, K. E. et al. Mol. Cell 73, 885–899.e6 (2019).

  20. 20.

    Li, J., Liang, W., Li, Y. & Qian, W. Plant Cell 30, 1954–1970 (2018).

Download references

Author information

Correspondence to Shan Yan.

Ethics declarations

Competing interests

The author declares no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark
Fig. 1: Apn2/APE2 suppresses Top1-induced mutations at rNMP sites.