ArticleNucleic acids research2019
A kinetochore-based ATM/ATR-independent DNA damage checkpoint maintains genomic integrity in trypanosomes.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
9 citing papers in PubMed, 20 citations in OpenAlex.
- Article
- Article
- ATR, a DNA damage kinase, modulates DNA replication timing in Leishmania major.PLoS genetics · 2025Article
- The cross talk of ubiquitination and chemotherapy tolerance in colorectal cancer.Journal of cancer research and clinical oncology · 2024Review
- Identification of a small-molecule inhibitor that selectively blocks DNA-binding by Trypanosoma brucei replication protein A1.Nature communications · 2023Article
- Life in plastic, it's fantastic! HowFrontiers in cellular and infection microbiology · 2023Review
- Systematic functional analysis of Leishmania protein kinases identifies regulators of differentiation or survival.Nature communications · 2021Article
- Trypanosome KKIP1 Dynamically Links the Inner Kinetochore to a Kinetoplastid Outer Kinetochore Complex.Frontiers in cellular and infection microbiology · 2021Article
- Identification of four unconventional kinetoplastid kinetochore proteins KKT22-25 inOpen biology · 2019Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
DNA damage-induced cell cycle checkpoints serve as surveillance mechanisms to maintain genomic stability, and are regulated by ATM/ATR-mediated signaling pathways that are conserved from yeast to humans. Trypanosoma brucei, an early divergent microbial eukaryote, lacks key components of the conventional DNA damage-induced G2/M cell cycle checkpoint and the spindle assembly checkpoint, and nothing is known about how T. brucei controls its cell cycle checkpoints. Here we discover a kinetochore-based, DNA damage-induced metaphase checkpoint in T. brucei. MMS-induced DNA damage triggers a metaphase arrest by modulating the abundance of the outer kinetochore protein KKIP5 in an Aurora B kinase- and kinetochore-dependent, but ATM/ATR-independent manner. Overexpression of KKIP5 arrests cells at metaphase through stabilizing the mitotic cyclin CYC6 and the cohesin subunit SCC1, mimicking DNA damage-induced metaphase arrest, whereas depletion of KKIP5 alleviates the DNA damage-induced metaphase arrest and causes chromosome mis-segregation and aneuploidy. These findings suggest that trypanosomes employ a novel DNA damage-induced metaphase checkpoint to maintain genomic integrity.
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Registered trials
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