Abstract
Panier et al. reveal that SLX4IP is a regulator of ALT telomere maintenance that binds to both BLM and SLX4 and influences the balance between resolution and dissolution at recombining telomeres. Its importance for the ALT process is underscored by the finding that SLX4IP is inactivated in a subset of ALT-positive osteosarcomas.
Original language | English |
---|---|
Pages (from-to) | 27-43.e11 |
Journal | MOLECULAR CELL |
Volume | 76 |
Issue number | 1 |
DOIs | |
Publication status | Published - 3 Oct 2019 |
Keywords
- ALT
- BLM
- cancer
- genome stability
- homologous recombination
- SLX4
- SLX4IP
- telomere
- XPF
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In: MOLECULAR CELL, Vol. 76, No. 1, 03.10.2019, p. 27-43.e11.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - SLX4IP Antagonizes Promiscuous BLM Activity during ALT Maintenance
AU - Panier, Stephanie
AU - Maric, Marija
AU - Hewitt, Graeme
AU - Mason-Osann, Emily
AU - Gali, Himabindu
AU - Dai, Anqi
AU - Labadorf, Adam
AU - Guervilly, Jean Hugues
AU - Ruis, Philip
AU - Segura-Bayona, Sandra
AU - Belan, Ondrej
AU - Marzec, Paulina
AU - Gaillard, Pierre Henri L.
AU - Flynn, Rachel L.
AU - Boulton, Simon J.
N1 - Funding Information: We would like to thank Grzegorz Sarek for valuable discussions, Jérôme Dejardin for providing the 2′F-RNA probes, John Rouse for providing the GFP-SLX4 construct, and Daniel Durocher for providing pcDNA5-FRT/TO-GFP and U2OS FLP/IN host cells. We thank Andrew Deans for very generously providing recombinant BLM protein. S.P., M.M., G.H., P.R., O.B., S.S.-B., and P.M. are supported by the Francis Crick Institute . S.P. was the recipient of a European Molecular Biology Organization (EMBO) Long Term Fellowship. Work in the P.-H.L.G. lab is supported by an Institut National Du Cancer (INCA) PLBIO 2016-159 grant. R.L.F. was supported by the National Center for Advancing Translational Sciences, NIH , through Boston University Clinical and Translational Science Institute (BU-CTSI) grant 1UL1TR001430 . Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH , 1R01CA201446-01A1 , an Edward Mallinckrodt Junior Foundation Award, and a Peter Paul Career Development Professorship from Boston University . E.M.-O. was supported by National Institute of General Medical Sciences (NIGMS) grant T32GM008541 . Work in the S.J.B. lab is supported by the Francis Crick Institute , which receives its core funding from Cancer Research UK ( FC0010048 ), the UK Medical Research Council ( FC0010048 ), and the Wellcome Trust ( FC0010048 ). S.J.B. is also the recipient of a European Research Council (ERC) Advanced Investigator Grant ( ERC-2017-ADG-742437 , “TelMetab”) and Wellcome Trust Senior Investigator and Collaborative Grants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding Information: We would like to thank Grzegorz Sarek for valuable discussions, J?r?me Dejardin for providing the 2?F-RNA probes, John Rouse for providing the GFP-SLX4 construct, and Daniel Durocher for providing pcDNA5-FRT/TO-GFP and U2OS FLP/IN host cells. We thank Andrew Deans for very generously providing recombinant BLM protein. S.P. M.M. G.H. P.R. O.B. S.S.-B. and P.M. are supported by the Francis Crick Institute. S.P. was the recipient of a European Molecular Biology Organization (EMBO) Long Term Fellowship. Work in the P.-H.L.G. lab is supported by an Institut National Du Cancer (INCA) PLBIO 2016-159 grant. R.L.F. was supported by the National Center for Advancing Translational Sciences, NIH, through Boston University Clinical and Translational Science Institute (BU-CTSI) grant 1UL1TR001430. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, 1R01CA201446-01A1, an Edward Mallinckrodt Junior Foundation Award, and a Peter Paul Career Development Professorship from Boston University. E.M.-O. was supported by National Institute of General Medical Sciences (NIGMS) grant T32GM008541. Work in the S.J.B. lab is supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC0010048), the UK Medical Research Council (FC0010048), and the Wellcome Trust (FC0010048). S.J.B. is also the recipient of a European Research Council (ERC) Advanced Investigator Grant (ERC-2017-ADG-742437, ?TelMetab?) and Wellcome Trust Senior Investigator and Collaborative Grants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. S.P. and S.J.B. conceived the project and wrote the manuscript with input from the other authors. M.M. performed the co-immunoprecipitation and immunoblotting experiments shown in Figures 5D?5F, S1S, S1W, S2D, S2E, S3D, S7D, and S7E. G.H. and P.M. performed PICh. G.H. generated cell lines and performed the microlaser irradiation experiment. P.R. performed FACS analysis. O.B. purified SLX4IP and performed the BLM helicase assay. S.S.-B. performed C-circle experiments. J.-H.G. and P.-H.L.G. performed SUMOylation assays. E.M.-O. H.G. A.L. and R.L.F. performed and analyzed all experiments shown in Figure 7 and Figure S7K. S.P. carried out all other experiments. The authors declare no competing interests. Publisher Copyright: © 2019 The Author(s)
PY - 2019/10/3
Y1 - 2019/10/3
N2 - Panier et al. reveal that SLX4IP is a regulator of ALT telomere maintenance that binds to both BLM and SLX4 and influences the balance between resolution and dissolution at recombining telomeres. Its importance for the ALT process is underscored by the finding that SLX4IP is inactivated in a subset of ALT-positive osteosarcomas.
AB - Panier et al. reveal that SLX4IP is a regulator of ALT telomere maintenance that binds to both BLM and SLX4 and influences the balance between resolution and dissolution at recombining telomeres. Its importance for the ALT process is underscored by the finding that SLX4IP is inactivated in a subset of ALT-positive osteosarcomas.
KW - ALT
KW - BLM
KW - cancer
KW - genome stability
KW - homologous recombination
KW - SLX4
KW - SLX4IP
KW - telomere
KW - XPF
UR - http://www.scopus.com/inward/record.url?scp=85072703232&partnerID=8YFLogxK
U2 - 10.1016/j.molcel.2019.07.010
DO - 10.1016/j.molcel.2019.07.010
M3 - Article
C2 - 31447390
AN - SCOPUS:85072703232
SN - 1097-2765
VL - 76
SP - 27-43.e11
JO - MOLECULAR CELL
JF - MOLECULAR CELL
IS - 1
ER -