ArticlePloS one2012
A novel role of human holliday junction resolvase GEN1 in the maintenance of centrosome integrity.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- ReducedInternational journal of molecular sciences · 2026Article
- Article
- Role of Bile-Derived Extracellular Vesicles in Hepatocellular Proliferation after Partial Hepatectomy in Rats.International journal of molecular sciences · 2023Article
- Disruption ofInternational journal of biological sciences · 2018Article
- Resolvase OsGEN1 Mediates DNA Repair by Homologous Recombination.Plant physiology · 2017Article
- Effect of GEN1 interference on the chemosensitivity of the breast cancer MCF-7 and SKBR3 cell lines.Oncology letters · 2016Article
- Whole-exome sequencing of a rare case of familial childhood acute lymphoblastic leukemia reveals putative predisposing mutations in Fanconi anemia genes.BMC cancer · 2015Article
- DNA damage during the G0/G1 phase triggers RNA-templated, Cockayne syndrome B-dependent homologous recombination.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- A novel strategy for targeted killing of tumor cells: Induction of multipolar acentrosomal mitotic spindles with a quinazolinone derivative mdivi-1.Molecular oncology · 2015Article
- Spatial control of the GEN1 Holliday junction resolvase ensures genome stability.Nature communications · 2014Article
- Holliday junction resolvases.Cold Spring Harbor perspectives in biology · 2014Review
- AtGEN1 and AtSEND1, two paralogs in Arabidopsis, possess holliday junction resolvase activity.Plant physiology · 2014Article
- Trinucleotide expansion in disease: why is there a length threshold?Current opinion in genetics & development · 2014Review
- Resolving branched DNA intermediates with structure-specific nucleases during replication in eukaryotes.Chromosoma · 2013Review
- Integrative multi-omics analysis-based Mendelian randomization identifies association of DNA repair-related genes with oral cancer.Cancer biomarkers : section A of Disease markersArticle
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The maintenance of genomic stability requires accurate genome replication, repair of DNA damage, and the precise segregation of chromosomes in mitosis. GEN1 possesses Holliday junction resolvase activity in vitro and presumably functions in homology driven repair of DNA double strand breaks. However, little is currently known about the cellular functions of human GEN1. In the present study we demonstrate that GEN1 is a novel centrosome associated protein and we characterize the various phenotypes associated with GEN1 deficiency. We identify an N-terminal centrosome localization signal in GEN1, which is required and sufficient for centrosome localization. We report that GEN1 depletion results in aberrant centrosome numbers associated with the formation of multiple spindle poles in mitosis, an increased number of cells with multi-nuclei, increased apoptosis and an elevated level of spontaneous DNA damage. We find homologous recombination severely impaired in GEN1 deficient cells, suggesting that GEN1 functions as a Holliday junction resolvase in vivo as well as in vitro. Complementation of GEN1 depleted cells with various GEN1 constructs revealed that centrosome association but not catalytic activity of GEN1 is required for preventing centrosome hyper-amplification, formation of multiple mitotic spindles, and multi-nucleation. Our findings provide novel insight into the biological functions of GEN1 by uncovering an important role of GEN1 in the regulation of centrosome integrity.
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