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Identification of candidate alternative lengthening of telomeres genes by methionine restriction and RNA interference.
Oncogene. 2007 Jul 12; 26(32):4635-47.O

Abstract

Telomerase-negative cancer cells can maintain their telomeres by a recombination-mediated alternative lengthening of telomeres (ALT) process. We reported previously that sequestration of MRE11/RAD50/NBS1 complexes represses ALT-mediated telomere length maintenance, and suppresses formation of ALT-associated promyelocytic leukemia (PML) bodies (APBs). APBs are PML bodies containing telomeric DNA and telomere-binding proteins, and are observed only in a small fraction of cells within asynchronously dividing ALT-positive cell populations. Here, we report that methionine restriction caused a reversible arrest in G0/G1 phase of the cell cycle and reversible induction of APB formation in most cells within an ALT-positive population. We combined methionine restriction with RNA interference to test whether the following proteins are required for APB formation: PML body-associated proteins, PML and Sp100; telomere-associated proteins, TRF1, TRF2, TIN2 and RAP1; and DNA repair proteins, MRE11, RAD50, NBS1 and 53BP1. APB formation was not decreased by depletion of Sp100 (as reported previously) or of 53BP1, although 53BP1 partially colocalizes with APBs. Depletion of the other proteins suppressed APB formation. Because of the close linkage between ALT-mediated telomere maintenance and ability to form APBs, the eight proteins identified by this screen as being required for APB formation are also likely to be required for the ALT mechanism.

Authors+Show Affiliations

Cancer Research Unit, Children's Medical Research Institute, Westmead, NSW, Australia.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17297460

Citation

Jiang, W-Q, et al. "Identification of Candidate Alternative Lengthening of Telomeres Genes By Methionine Restriction and RNA Interference." Oncogene, vol. 26, no. 32, 2007, pp. 4635-47.
Jiang WQ, Zhong ZH, Henson JD, et al. Identification of candidate alternative lengthening of telomeres genes by methionine restriction and RNA interference. Oncogene. 2007;26(32):4635-47.
Jiang, W. Q., Zhong, Z. H., Henson, J. D., & Reddel, R. R. (2007). Identification of candidate alternative lengthening of telomeres genes by methionine restriction and RNA interference. Oncogene, 26(32), 4635-47.
Jiang WQ, et al. Identification of Candidate Alternative Lengthening of Telomeres Genes By Methionine Restriction and RNA Interference. Oncogene. 2007 Jul 12;26(32):4635-47. PubMed PMID: 17297460.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of candidate alternative lengthening of telomeres genes by methionine restriction and RNA interference. AU - Jiang,W-Q, AU - Zhong,Z-H, AU - Henson,J D, AU - Reddel,R R, Y1 - 2007/02/05/ PY - 2007/2/14/pubmed PY - 2007/8/19/medline PY - 2007/2/14/entrez SP - 4635 EP - 47 JF - Oncogene JO - Oncogene VL - 26 IS - 32 N2 - Telomerase-negative cancer cells can maintain their telomeres by a recombination-mediated alternative lengthening of telomeres (ALT) process. We reported previously that sequestration of MRE11/RAD50/NBS1 complexes represses ALT-mediated telomere length maintenance, and suppresses formation of ALT-associated promyelocytic leukemia (PML) bodies (APBs). APBs are PML bodies containing telomeric DNA and telomere-binding proteins, and are observed only in a small fraction of cells within asynchronously dividing ALT-positive cell populations. Here, we report that methionine restriction caused a reversible arrest in G0/G1 phase of the cell cycle and reversible induction of APB formation in most cells within an ALT-positive population. We combined methionine restriction with RNA interference to test whether the following proteins are required for APB formation: PML body-associated proteins, PML and Sp100; telomere-associated proteins, TRF1, TRF2, TIN2 and RAP1; and DNA repair proteins, MRE11, RAD50, NBS1 and 53BP1. APB formation was not decreased by depletion of Sp100 (as reported previously) or of 53BP1, although 53BP1 partially colocalizes with APBs. Depletion of the other proteins suppressed APB formation. Because of the close linkage between ALT-mediated telomere maintenance and ability to form APBs, the eight proteins identified by this screen as being required for APB formation are also likely to be required for the ALT mechanism. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/17297460/Identification_of_candidate_alternative_lengthening_of_telomeres_genes_by_methionine_restriction_and_RNA_interference_ L2 - http://dx.doi.org/10.1038/sj.onc.1210260 DB - PRIME DP - Unbound Medicine ER -