Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Human SNM1B is required for normal cellular response to both DNA interstrand crosslink-inducing agents and ionizing radiation

Oncogene volume 23, pages 8611–8618 (2004)Cite this article

Abstract

DNA interstrand crosslinks (ICLs) are critical lesions for the mammalian cell since they affect both DNA strands and block transcription and replication. The repair of ICLs in the mammalian cell involves components of different repair pathways such as nucleotide-excision repair and the double-strand break/homologous recombination repair pathways. However, the mechanistic details of mammalian ICL repair have not been fully delineated. We describe here the complete coding sequence and the genomic organization of hSNM1B, one of at least three human homologs of the Saccharomyces cerevisiae PSO2 gene. Depletion of hSNM1B by RNA interference rendered cells hypersensitive to ICL-inducing agents. This requirement for hSNM1B in the cellular response to ICL has been hypothesized before but never experimentally verified. In addition, siRNA knockdown of hSNM1B rendered cells sensitive to ionizing radiation, suggesting the possibility of hSNM1B involvement in homologous recombination repair of double-strand breaks arising as intermediates of ICL repair. Monoubiquitination of FANCD2, a key step in the FANC/BRCA pathway, is not affected in hSNM1B-depleted HeLa cells, indicating that hSNM1B is probably not a part of the Fanconi anemia core complex. Nonetheless, similarities in the phenotype of hSNM1B-depleted cells and cultured cells from patients suffering from Fanconi anemia make hSNM1B a candidate for one of the as yet unidentified Fanconi anemia genes not involved in monoubiquitination of FANCD2.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Brendel M, Bonatto D, Strauss M, Revers LF, Pungartnik C, Saffi J and Henriques JAP . (2003). Mutat. Res. Rev. Mutat. Res., 544, 179–193.

  • Bruun D, Folias A, Akkari Y, Cox Y, Olson S and Moses R . (2003). DNA Repair, 2, 1007–1013.

  • Caldecott K and Jeggo P . (1991). Mutat. Res., 255, 111–121.

  • Callebaut I, Moshous D, Mornon JP and De Villartay JP . (2002). Nucleic Acids Res., 30, 3592–3601.

  • Carreau M, Alon N, Bosnoyan-Collins L, Joenje H and Buchwald M . (1999). Mutat. Res. DNA Repair, 435, 103–109.

  • Cassier C, Chanet R, Henriques JA and Moustacchi E . (1980). Genetics, 96, 841–857.

  • Cassier-Chauvat C and Moustacchi E . (1988). Curr. Genet., 13, 37–40.

  • Cerosaletti KM and Concannon P . (2003). J. Biol. Chem., 278, 21944–21951.

  • D'Andrea AD and Grompe M . (2003). Nat. Rev. Cancer, 3, 23–34.

  • De Silva IU, McHugh PJ, Clingen PH and Hartley JA . (2000). Mol. Cell. Biol., 20, 7980–7990.

  • de Winter JP, Leveille F, van Berkel CGM, Rooimans MA, van der Weel L, Steltenpool J, Demuth I, Morgan NV, Alon N, Bosnoyan-Collins L, Lightfoot J, Leegwater PA, Waisfisz Q, Komatsu K, Arwert F, Pronk JC, Mathew CG, Digweed M, Buchwald M and Joenje H . (2000a). Am. J. Hum. Genet., 67, 1306–1308.

  • de Winter JP, Rooimans MA, van der Weel L, van Berkel CGM, Alon N, Bosnoyan-Collins L, de Groot J, Zhi Y, Waisfisz Q, Pronk JC, Arwert F, Mathew CG, Scheper RJ, Hoatlin ME, Buchwald M and Joenje H . (2000b). Nat. Genet., 24, 15–16.

  • de Winter JP, Waisfisz Q, Rooimans MA, van Berkel CGM, Bosnoyan-Collins L, Alon N, Carreau M, Bender O, Demuth I, Schindler D, Pronk JC, Arwert F, Hoehn H, Digweed M, Buchwald M and Joenje H . (1998). Nat. Genet., 20, 281–283.

  • Demuth I and Digweed M . (1998). Mutat. Res. DNA Repair, 409, 11–16.

  • Digweed M, Demuth I, Rothe S, Scholz R, Jordan A, Grotzinger C, Schindler D, Grompe M and Sperling K . (2002). Oncogene, 21, 4873–4878.

  • DiTullio RA, Mochan TA, Venere M, Bartkova J, Sehested M, Bartek J and Halazonetis TD . (2002). Nat. Cell Biol., 4, 998–1002.

  • Dronkert MLG, de Wit J, Boeve M, Vasconcelos ML, van Steeg H, Tan TLR, Hoeijmakers JHJ and Kanaar R . (2000). Mol. Cell. Biol., 20, 4553–4561.

  • Elbashir SM, Harborth J, Weber K and Tuschl T . (2002). Methods, 26, 199–213.

  • Essers J, Hendriks RW, Swagemakers SMA, Troelstra C, deWit J, Bootsma D, Hoeijmakers JHJ and Kanaar R . (1997). Cell, 89, 195–204.

  • Garcia-Higuera I, Taniguchi T, Ganesan S, Meyn MS, Timmers C, Hejna J, Grompe M and D'Andrea AD . (2001). Mol. Cell, 7, 249–262.

  • Gatti RA . (2001). Acta Oncol., 40, 702–711.

  • Henriques JAP and Moustacchi E . (1980). Genetics, 95, 273–288.

  • Howlett NG, Taniguchi T, Olson S, Cox B, Waisfisz Q, Die-Smulders C, Persky N, Grompe M, Joenje H, Pals G, Ikeda H, Fox EA and D'Andrea AD . (2002). Science, 297, 606–609.

  • Jachymczyk WJ, Vonborstel RC, Mowat MRA and Hastings PJ . (1981). Mol. Gen. Genet., 182, 196–205.

  • Jenny A, Minvielle-Sebastia L, Preker PJ and Keller W . (1996). Science, 274, 1514–1517.

  • Joenje H and Patel KJ . (2001). Nat. Rev. Genet., 2, 446–457.

  • Levitus M, Rooimans MA, Steltenpool J, Cool NF, Oostra AB, Mathew CG, Hoatlin ME, Waisfisz Q, Arwert F, de Winter JP and Joenje H . (2003). Blood, 103, 2498–2503.

  • Lo Len Foe JR, Rooimans MA, Bosnoyan-Collins L, Alon N, Wijker M, Parker L, Lightfoot J, Carreau M, Callen DF, Savoia A, Cheng NC, vanBerkel CGM, Strunk MHP, Gille JJP, Pals G, Kruyt FAE, Pronk JC, Arwert F, Buchwald M and Joenje H . (1996). Nat. Genet., 14, 488–488.

  • Ma YM, Pannicke U, Schwarz K and Lieber MR . (2002). Cell, 108, 781–794.

  • Magana-Schwencke N, Henriques JAP, Chanet R and Moustacchi E . (1982). Proc. Natl. Acad. Sci. USA Biol. Sci., 79, 1722–1726.

  • McHugh PJ, Sones WR and Hartley JA . (2000). Mol. Cell. Biol., 20, 3425–3433.

  • McHugh PJ, Spanswick VJ and Hartley JA . (2001). Lancet Oncol., 2, 483–490.

  • Meetei AR, de Winter JP, Medhurst AL, Wallisch M, Waisfisz Q, van de Vrugt HJ, Oostra AB, Yan ZJ, Ling C, Bishop CE, Hoatlin ME, Joenje H and Wang WD . (2003). Nat. Genet., 35, 165–170.

  • Moshous D, Callebaut I, De Chasseval R, Corneo B, Cavazzana-Calvo M, le Deist F, Tezcan I, Sanal O, Bertrand Y, Philippe N, Fischer A and De Villartay JP . (2001). Cell, 105, 177–186.

  • Moynahan ME, Cui TY and Jasin M . (2001). Cancer Res., 61, 4842–4850.

  • Nagase T, Miyajima N, Tanaka A, Sazuka T, Seki N, Sato S, Tabata S, Ishikawa K, Kawarabayasi Y and Kotani H . (1995). DNA Res., 2, 37–43.

  • Patel KJ, Yu VPCC, Lee HS, Corcoran A, Thistlethwaite FC, Evans MJ, Colledge WH, Friedman LS, Ponder BAJ and Venkitaraman AR . (1998). Mol. Cell, 1, 347–357.

  • Richie CT, Peterson C, Lu T, Hittelman WN, Carpenter PB and Legerski RJ . (2002). Mol. Cell. Biol., 22, 8635–8647.

  • Richter D, Niegemann E and Brendel M . (1992). Mol. Gen. Genet., 231, 194–200.

  • Rooney S, Sekiguchi J, Zhu CM, Cheng HL, Manis J, Whitlow S, DeVido J, Foy D, Chaudhuri J, Lombard D and Alt FW . (2002). Mol. Cell, 10, 1379–1390.

  • Rothfuss A and Grompe M . (2004). Mol. Cell Biol., 24, 123–124.

  • Strathdee CA, Gavish H, Shannon WR and Buchwald M . (1992). Nature, 356, 763–767.

  • Tavtigian SV, Simard J, Teng D H F, Abtin V, Baumgard M, Beck A, Camp NJ, Carillo AR, Chen Y, Dayananth P, Desrochers M, Dumont M, Farnham JM, Frank D, Frye C, Ghaffari S, Gupte JS, Hu R, Iliev D, Janecki T, Kort EN, Laity KE, Leavitt A, Leblanc G, McArthur-Morrison J, Pederson A, Penn B, Peterson KT, Reid JE, Richards S, Schroeder M, Smith R, Snyder SC, Swedlund B, Swensen J, Thomas A, Tranchant M, Woodland AM, Labrie F, Skolnick MH, Neuhausen S, Rommens J and Cannon-Albright LA . (2001). Nat. Genet., 27, 172–180.

  • The Fanconi anaemia/breast cancer consortium (1996). Nat. Genet., 14, 324–328.

  • Timmers C, Taniguchi T, Hejna J, Reifsteck C, Lucas L, Bruun D, Thayer M, Cox B, Olson S, D'Andrea AD, Moses R and Grompe M . (2001). Mol. Cell, 7, 241–248.

  • Tutt A, Gabriel A, Bertwistle D, Connor F, Paterson H, Peacock J, Ross G and Ashworth A . (1999). Curr. Biol., 9, 1107–1110.

  • Wilborn F and Brendel M . (1989). Curr. Genet., 16, 331–338.

Download references

Acknowledgements

This work was supported by a grant from the National Cancer Institute (CA57569). ID was also supported, in part, by a grant from the Deutsche Forschungsgemeinschaft (Forschungsstipendium). We thank Lemuel Navarro and Anne Morrison for assistance with nucleotide sequencing, Karen Cerosaletti for critical comments on the manuscript, Mary West for assistance in manuscript preparation and Thanos Halazonetis for kindly providing the 53BP1 monoclonal antibody.

Author information

Authors and Affiliations

  1. Molecular Genetics Program, Benaroya Research Institute, Seattle, 98101-2795, WA, USA

    Ilja Demuth & Patrick Concannon

  2. Department of Immunology, University of Washington School of Medicine, Seattle, 98195, WA, USA

    Ilja Demuth & Patrick Concannon

  3. Institut fuer Humangenetik, Charité-Campus Virchow Klinikum, Humboldt Universitaet zu Berlin, Augustenburger Platz 1, Berlin, 13353, Germany

    Martin Digweed

Authors
  1. Ilja Demuth
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Martin Digweed
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Patrick Concannon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Patrick Concannon.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Demuth, I., Digweed, M. & Concannon, P. Human SNM1B is required for normal cellular response to both DNA interstrand crosslink-inducing agents and ionizing radiation. Oncogene 23, 8611–8618 (2004). https://doi.org/10.1038/sj.onc.1207895

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1207895

Keywords

This article is cited by

Search

Advanced search

Quick links