ArticleMolecular biology of the cell2007
Increased common fragile site expression, cell proliferation defects, and apoptosis following conditional inactivation of mouse Hus1 in primary cultured cells.
Article in Molecular biology of the cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Article
- Common fragile sites: protection and repair.Cell & bioscience · 2020Review
- A tough row to hoe: when replication forks encounter DNA damage.Biochemical Society transactions · 2018Review
- Fragile sites in cancer: more than meets the eye.Nature reviews. Cancer · 2017Review
- DNA secondary structure at chromosomal fragile sites in human disease.Current genomics · 2015Article
- In vitro and in vivo effects of graphene oxide and reduced graphene oxide on glioblastoma.International journal of nanomedicine · 2015Article
- Are common fragile sites merely structural domains or highly organized "functional" units susceptible to oncogenic stress?Cellular and molecular life sciences : CMLS · 2014Review
- Interplay between genetic and epigenetic factors governs common fragile site instability in cancer.Cellular and molecular life sciences : CMLS · 2014Review
- Replication fork recovery and regulation of common fragile sites stability.Cellular and molecular life sciences : CMLS · 2014Review
- Article
- In vitro evaluation of the effects of graphene platelets on glioblastoma multiforme cells.International journal of nanomedicine · 2013Article
- Genome instability at common fragile sites: searching for the cause of their instability.BioMed research international · 2013Review
- Disease severity in a mouse model of ataxia telangiectasia is modulated by the DNA damage checkpoint gene Hus1.Human molecular genetics · 2012Article
- The RAD9-RAD1-HUS1 (9.1.1) complex interacts with WRN and is crucial to regulate its response to replication fork stalling.Oncogene · 2012Article
- Common fragile sites: genomic hotspots of DNA damage and carcinogenesis.International journal of molecular sciences · 2012Review
- UHRF1 depletion causes a G2/M arrest, activation of DNA damage response and apoptosis.The Biochemical journal · 2011Article
- DNA instability at chromosomal fragile sites in cancer.Current genomics · 2010Article
- ATR preferentially interacts with common fragile site FRA3B and the binding requires its kinase activity in response to aphidicolin treatment.Mutation research · 2010Article
- Removing all obstacles: a critical role for p53 in promoting tissue renewal.Cell cycle (Georgetown, Tex.) · 2010Review
- Dual inactivation of Hus1 and p53 in the mouse mammary gland results in accumulation of damaged cells and impaired tissue regeneration.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Targeted disruption of the mouse Hus1 cell cycle checkpoint gene results in embryonic lethality and proliferative arrest in cultured cells. To investigate the essential functions of Hus1, we developed a system for the regulated inactivation of mouse Hus1 in primary fibroblasts. Inactivation of a loxP site-flanked conditional Hus1 allele by using a cre-expressing adenovirus resulted in reduced cell doubling, cell cycle alterations, and increased apoptosis. These phenotypes were associated with a significantly increased frequency of gross chromosomal abnormalities and an S-phase-specific accumulation of phosphorylated histone H2AX, an indicator of double-stranded DNA breaks. To determine whether these chromosomal abnormalities occurred randomly or at specific genomic regions, we assessed the stability of common fragile sites, chromosomal loci that are prone to breakage in cells undergoing replication stress. Hus1 was found to be essential for fragile site stability, because spontaneous chromosomal abnormalities occurred preferentially at common fragile sites upon conditional Hus1 inactivation. Although p53 levels increased after Hus1 loss, deletion of p53 failed to rescue the cell-doubling defect or increased apoptosis in conditional Hus1 knockout cells. In summary, we propose that Hus1 loss leads to chromosomal instability during DNA replication, triggering increased apoptosis and impaired proliferation through p53-independent mechanisms.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.