The involvement of active DNA synthesis in camptothecin-induced G2 arrest: Altered regulation of p34(cdc2)/cyclin B

Y. P. Tsao, P. D'Arpa, Leroy-Fong Liu

Research output: Contribution to journalArticle

226 Citations (Scopus)

Abstract

Cell cycle arrest in G2 phase is a common response to a variety of DNA- damaging agents. The coupling between DNA damage and G2 arrest was studied in synchronized HeLa cells using camptothecin, a highly specific inhibitor of topoisomerase I that damages DNA through the formation of reversible topoisomerase I-DNA cleavable complexes. Brief camptothecin treatment of early S-phase HeLa cells caused arrest at G2 phase and abolished the activation of p34(cdc2) protein kinase. Both tyrosine dephosphorylation of p34(cdc2) and cyclin B accumulation were altered. These cell cycle-dependent changes were not observed when DNA replication was inhibited by aphidicolin during the brief camptothecin treatment. Our results suggest that to produce G2 arrest, active DNA synthesis is required at the time of camptothecin treatment, as was previously shown for camptothecin-induced cytotoxicity. Furthermore, our results suggest that the interaction of the replication fork with DNA damage may ultimately trigger altered regulation of p34(cdc2)/cyclin B, leading to cell cycle arrest at the G2 phase.

Original languageEnglish
Pages (from-to)1823-1829
Number of pages7
JournalCancer Research
Volume52
Issue number7
Publication statusPublished - 1992
Externally publishedYes

Fingerprint

Cyclin B
Camptothecin
G2 Phase
DNA
Cell Cycle Checkpoints
HeLa Cells
DNA Damage
CDC2 Protein Kinase
Topoisomerase I Inhibitors
Aphidicolin
Type I DNA Topoisomerase
DNA Replication
S Phase
Protein Kinases
Tyrosine
Cell Cycle

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

The involvement of active DNA synthesis in camptothecin-induced G2 arrest : Altered regulation of p34(cdc2)/cyclin B. / Tsao, Y. P.; D'Arpa, P.; Liu, Leroy-Fong.

In: Cancer Research, Vol. 52, No. 7, 1992, p. 1823-1829.

Research output: Contribution to journalArticle

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