English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  SLX4IP Antagonizes Promiscuous BLM Activity during ALT Maintenance

Panier, S., Maric, M., Hewitt, G., Mason-Osann, E., Gali, H., Dai, A., et al. (2019). SLX4IP Antagonizes Promiscuous BLM Activity during ALT Maintenance. Mol Cell, 76(1), 27-43 e11. doi:10.1016/j.molcel.2019.07.010.

Item is

Files

show Files

Locators

show
hide
Description:
-
OA-Status:
Not specified

Creators

show
hide
 Creators:
Panier, S.1, Author           
Maric, M., Author
Hewitt, G., Author
Mason-Osann, E., Author
Gali, H., Author
Dai, A., Author
Labadorf, A., Author
Guervilly, J. H., Author
Ruis, P., Author
Segura-Bayona, S., Author
Belan, O., Author
Marzec, P., Author
Gaillard, P. H. L., Author
Flynn, R. L., Author
Boulton, S. J., Author
Affiliations:
1Panier – Genome Instability and Ageing, Max Planck Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_3394004              

Content

show
hide
Free keywords: Animals Bone Neoplasms/*enzymology/genetics/pathology Carrier Proteins/genetics/*metabolism Cell Proliferation DNA-Binding Proteins/genetics/metabolism Female Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic HEK293 Cells HeLa Cells Humans Mice, Knockout Mice, SCID Osteosarcoma/*enzymology/genetics/pathology Protein Binding Protein Interaction Domains and Motifs RecQ Helicases/genetics/*metabolism Recombinases/genetics/metabolism Signal Transduction Telomere/genetics/*metabolism/pathology *Telomere Homeostasis *alt *blm *slx4 *slx4ip *xpf *cancer *genome stability *homologous recombination *telomere
 Abstract: Cancer cells acquire unlimited proliferative capacity by either re-expressing telomerase or inducing alternative lengthening of telomeres (ALT), which relies on telomere recombination. Here, we show that ALT recombination requires coordinate regulation of the SMX and BTR complexes to ensure the appropriate balance of resolution and dissolution activities at recombining telomeres. Critical to this control is SLX4IP, which accumulates at ALT telomeres and interacts with SLX4, XPF, and BLM. Loss of SLX4IP increases ALT-related phenotypes, which is incompatible with cell growth following concomitant loss of SLX4. Inactivation of BLM is sufficient to rescue telomere aggregation and the synthetic growth defect in this context, suggesting that SLX4IP favors SMX-dependent resolution by antagonizing promiscuous BLM activity during ALT recombination. Finally, we show that SLX4IP is inactivated in a subset of ALT-positive osteosarcomas. Collectively, our findings uncover an SLX4IP-dependent regulatory mechanism critical for telomere maintenance in ALT cancer cells.

Details

show
hide
Language(s):
 Dates: 2019-10-032019-08-27
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: Other: 31447390
DOI: 10.1016/j.molcel.2019.07.010
ISSN: 1097-4164 (Electronic)1097-2765 (Linking)
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Mol Cell
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 76 (1) Sequence Number: - Start / End Page: 27 - 43 e11 Identifier: -