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SUMO ‐targeted ubiquitin ligase RNF 4 plays a critical role in preventing chromosome loss
Author(s) -
Hirota Kouji,
Tsuda Masataka,
Murai Junko,
Takagi Tokiyo,
Keka Islam Shamima,
Narita Takeo,
Fujita Mari,
Sasanuma Hiroyuki,
Kobayashi Junya,
Takeda Shunichi
Publication year - 2014
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12173
Subject(s) - ubiquitin ligase , biology , ubiquitin , dna ligase , microbiology and biotechnology , genetics , dna , gene
RING finger protein 4 ( RNF 4) represents a subclass of ubiquitin ligases that target proteins modified by the small ubiquitin‐like modifier ( SUMO ) for ubiquitin‐mediated degradation. We disrupted the RNF 4 gene in chicken DT 40 cells and found that the resulting RNF 4 −/− cells gradually lost proliferation capability. Strikingly, this compromised proliferation was associated with an unprecedented cellular effect: the gradual decrease in the number of intact chromosomes. In the 6 weeks after gene targeting, there was a 25% reduction in the DNA content of the RNF 4 −/− cells. Regarding trisomic chromosome 2, 60% of the RNF 4 −/− cells lost one homologue, suggesting that DNA loss was mediated by whole chromosome loss. To determine the cause of this chromosome loss, we examined cell‐cycle checkpoint pathways. RNF 4 −/− cells showed a partial defect in the spindle assembly checkpoint, premature dissociation of sister chromatids, and a marked increase in the number of lagging chromosomes at anaphase. Thus, combined defects in SAC and sister chromatid cohesion may result in increased lagging chromosomes, leading to chromosome loss without accompanying chromosome gain in RNF 4 −/− cells. We therefore propose that RNF 4 plays a novel role in preventing the loss of intact chromosomes and ensures the maintenance of chromosome integrity.