DNA C-circles Are Specific and Quantifiable Markers of Alternative-lengthening-of-telomeres Activity

Overview

Journal Nat Biotechnol

Specialty Biotechnology

Date 2009 Nov 26

PMID 19935656

Citations 285

Authors

Jeremy D Henson

Ying Cao

Lily I Huschtscha

Andy C Chang

Amy Y M Au

Hilda A Pickett

Roger R Reddel

Affiliations

Soon will be listed here.

Abstract

Alternative lengthening of telomeres (ALT) is likely to be an important target for anticancer treatment as approximately 10% of cancers depend on this telomere maintenance mechanism for continued growth, and inhibition of ALT can cause cellular senescence. However, no ALT inhibitors have been developed for therapeutic use because of the lack of a suitable ALT activity assay and of known ALT-specific target molecules. Here we show that partially single-stranded telomeric (CCCTAA)(n) DNA circles (C-circles) are ALT specific. We provide an assay that is rapidly and linearly responsive to ALT activity and that is suitable for screening for ALT inhibitors. We detect C-circles in blood from ALT(+) osteosarcoma patients, suggesting that the C-circle assay (CC assay) may have clinical utility for diagnosis and management of ALT(+) tumors.

Citing Articles

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Chang S, Tan J, Bao R, Zhang Y, Tong J, Jia T Cell Biosci. 2025; 15(1):31.

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The single-stranded DNA-binding factor SUB1/PC4 alleviates replication stress at telomeres and is a vulnerability of ALT cancer cells.

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Copy-number dosage regulates telomere maintenance and disease-associated pathways in neuroblastoma.

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