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Title: Interference in DNA Replication Can Cause Mitotic Chromosomal Breakage Unassociated with Double-Strand Breaks
Authors: Fujita, Mari
Sasanuma, Hiroyuki  kyouindb  KAKEN_id
Yamamoto, Kimiyo N.
Harada, Hiroshi  kyouindb  KAKEN_id  orcid (unconfirmed)
Kurosawa, Aya
Adachi, Noritaka
Omura, Masato
Hiraoka, Masahiro  KAKEN_id
Takeda, Shunichi  kyouindb  KAKEN_id
Hirota, Kouji
Author's alias: 廣田, 耕志
Issue Date: 3-Apr-2013
Publisher: Public Library of Science
Journal title: PLoS ONE
Volume: 8
Issue: 4
Thesis number: e60043
Abstract: Morphological analysis of mitotic chromosomes is used to detect mutagenic chemical compounds and to estimate the dose of ionizing radiation to be administered. It has long been believed that chromosomal breaks are always associated with double-strand breaks (DSBs). We here provide compelling evidence against this canonical theory. We employed a genetic approach using two cell lines, chicken DT40 and human Nalm-6. We measured the number of chromosomal breaks induced by three replication-blocking agents (aphidicolin, 5-fluorouracil, and hydroxyurea) in DSB-repair-proficient wild-type cells and cells deficient in both homologous recombination and nonhomologous end-joining (the two major DSB-repair pathways). Exposure of cells to the three replication-blocking agents for at least two cell cycles resulted in comparable numbers of chromosomal breaks for RAD54−/−/KU70−/− DT40 clones and wild-type cells. Likewise, the numbers of chromosomal breaks induced in RAD54−/−/LIG4−/− Nalm-6 clones and wild-type cells were also comparable. These data indicate that the replication-blocking agents can cause chromosomal breaks unassociated with DSBs. In contrast with DSB-repair-deficient cells, chicken DT40 cells deficient in PIF1 or ATRIP, which molecules contribute to the completion of DNA replication, displayed higher numbers of mitotic chromosomal breaks induced by aphidicolin than did wild-type cells, suggesting that single-strand gaps left unreplicated may result in mitotic chromosomal breaks.
Description: DNAが切れていないのに発生する染色体断裂の発見 -ヒトの被爆線量を測定する手法に異議あり-. 京都大学プレスリリース. 2013-04-04.
Rights: © 2013 Fujita et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI(Published Version): 10.1371/journal.pone.0060043
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