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A critical role of telomere chromatin compaction in ALT tumor cell growth.

ABSTRACT: ALT tumor cells often contain abundant DNA damage foci at telomeres and rely on the alternative lengthening of telomeres (ALT) mechanism to maintain their telomeres. How the telomere chromatin is regulated and maintained in these cells remains largely unknown. In this study, we present evidence that heterochromatin protein 1 binding protein 3 (HP1BP3) can localize to telomeres and is particularly enriched on telomeres in ALT cells. HP1BP3 inhibition led to preferential growth inhibition of ALT cells, which was accompanied by telomere chromatin decompaction, increased presence of C-circles, more pronounced ALT-associated phenotypes and elongated telomeres. Furthermore, HP1BP3 appeared to participate in regulating telomere histone H3K9me3 epigenetic marks. Taken together, our data suggest that HP1BP3 functions on telomeres to maintain telomere chromatin and represents a novel target for inhibiting ALT cancer cells.

SUBMITTER: Shi G

PROVIDER: S-EPMC7293046 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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A critical role of telomere chromatin compaction in ALT tumor cell growth.

Shi Guang G Hu Yang Y Zhu Xing X Jiang Yuanling Y Pang Junjie J Wang Chuanle C Huang Wenjun W Zhao Yong Y Ma Wenbin W Liu Dan D Huang Junjiu J Songyang Zhou Z

Nucleic acids research 20200601 11

ALT tumor cells often contain abundant DNA damage foci at telomeres and rely on the alternative lengthening of telomeres (ALT) mechanism to maintain their telomeres. How the telomere chromatin is regulated and maintained in these cells remains largely unknown. In this study, we present evidence that heterochromatin protein 1 binding protein 3 (HP1BP3) can localize to telomeres and is particularly enriched on telomeres in ALT cells. HP1BP3 inhibition led to preferential growth inhibition of ALT c ...[more]

PMID: 32379321

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