Schizosaccharomyces pombe Assays to Study Mitotic Recombination Outcomes

Hylton, Hannah M; Lucas, Bailey E; Petreaca, Ruben C.

doi:10.3390/genes11010079

Cited by 3 publications

(2 citation statements)

References 178 publications

(220 reference statements)

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“…Traditionally, the yeast model system has been fundamental in unravelling mechanisms and pathways of DNA damage repair [ 72 , 73 ]. Although neither BRCA1 or BRCA2 are found in yeast, a yeast assay to characterize certain ectopically expressed human BRCA mutations has also been developed [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

Pan-cancer analysis of co-occurring mutations in RAD52 and the BRCA1-BRCA2-PALB2 axis in human cancers

et al. 2022

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In human cells homologous recombination (HR) is critical for repair of DNA double strand breaks (DSBs) and rescue of stalled or collapsed replication forks. HR is facilitated by RAD51 which is loaded onto DNA by either BRCA2-BRCA1-PALB2 or RAD52. In human culture cells, double-knockdowns of RAD52 and genes in the BRCA1-BRCA2-PALB2 axis are lethal. Mutations in BRCA2, BRCA1 or PALB2 significantly impairs error free HR as RAD51 loading relies on RAD52 which is not as proficient as BRCA2-BRCA1-PALB2. RAD52 also facilitates Single Strand Annealing (SSA) that produces intra-chromosomal deletions. Some RAD52 mutations that affect the SSA function or decrease RAD52 association with DNA can suppress certain BRCA2 associated phenotypes in breast cancers. In this report we did a pan-cancer analysis using data reported on the Catalogue of Somatic Mutations in Cancers (COSMIC) to identify double mutants between RAD52 and BRCA1, BRCA2 or PALB2 that occur in cancer cells. We find that co-occurring mutations are likely in certain cancer tissues but not others. However, all mutations occur in a heterozygous state. Further, using computational and machine learning tools we identified only a handful of pathogenic or driver mutations predicted to significantly affect the function of the proteins. This supports previous findings that co-inactivation of RAD52 with any members of the BRCA2-BRCA1-PALB2 axis is lethal. Molecular modeling also revealed that pathogenic RAD52 mutations co-occurring with mutations in BRCA2-BRCA1-PALB2 axis are either expected to attenuate its SSA function or its interaction with DNA. This study extends previous breast cancer findings to other cancer types and shows that co-occurring mutations likely destabilize HR by similar mechanisms as in breast cancers.

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Section: Discussionmentioning

confidence: 99%

Pan-cancer analysis of co-occurring mutations in RAD52 and the BRCA1-BRCA2-PALB2 axis in human cancers

et al. 2022

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“…WT and cbf11Δ cells harboring the Ch16-RMGAH non-essential minichromosome (Hylton et al, 2020; Tinline-Purvis et al, 2009) were grown on YES plates with low adenine content (10 mg/l). Under such conditions, cells that have lost the minichromosome and thus are adenine auxotrophs ( ade6-M210 ) turn dark red.…”

Section: Methodsmentioning

confidence: 99%

Altered cohesin dynamics and histone H3K9 modifications contribute to mitotic defects in thecbf11Δlipid metabolism mutant

Vishwanatha

Princová

Hohoš

et al. 2022

Preprint

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Mitotic fidelity is crucial for the faithful distribution of genetic information into the daughter cells. Many fungal species, including the fission yeast Schizosaccharomyces pombe, undergo a closed form of mitosis, during which the nuclear envelope does not break down. In S. pombe numerous processes have been identified that contribute to successful completion of mitosis. Notably, perturbations of lipid metabolism can lead to catastrophic mitosis and the "cut" phenotype. It was suggested that these mitotic defects are caused by insufficient membrane phospholipid supply during the anaphase nuclear expansion. However, it is not clear whether additional factors are involved. In this study we characterized in detail the mitosis in an S. pombe mutant lacking the Cbf11 transcription factor, which regulates lipid metabolism genes. We show that in cbf11Δ cells mitotic defects appear already prior to anaphase, before the nuclear expansion begins. Moreover, we identify altered cohesin dynamics and centromeric chromatin structure as additional factors affecting mitotic fidelity in cells with disrupted lipid homeostasis, providing new insights into this fundamental biological process.

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Altered cohesin dynamics and H3K9 modifications contribute to mitotic defects in thecbf11Δlipid metabolism mutant

Vishwanatha

Princová

Hohoš

et al. 2023

Journal of Cell Science

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Mitotic fidelity is crucial for the faithful distribution of genetic information into the daughter cells. Many fungal species, including the fission yeast Schizosaccharomyces pombe, undergo a closed form of mitosis, during which the nuclear envelope does not break down. In S. pombe numerous processes have been identified that contribute to successful completion of mitosis. Notably, perturbations of lipid metabolism can lead to catastrophic mitosis and the “cut” phenotype. It was suggested that these mitotic defects are caused by insufficient membrane phospholipid supply during the anaphase nuclear expansion. However, it is not clear whether additional factors are involved. In this study we characterized in detail the mitosis in an S. pombe mutant lacking the Cbf11 transcription factor, which regulates lipid metabolism genes. We show that in cbf11Δ cells mitotic defects appear already prior to anaphase, before the nuclear expansion begins. Moreover, we identify altered cohesin dynamics and centromeric chromatin structure as additional factors affecting mitotic fidelity in cells with disrupted lipid homeostasis, providing new insights into this fundamental biological process.

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Schizosaccharomyces pombe Assays to Study Mitotic Recombination Outcomes

Cited by 3 publications

References 178 publications

Pan-cancer analysis of co-occurring mutations in RAD52 and the BRCA1-BRCA2-PALB2 axis in human cancers

Pan-cancer analysis of co-occurring mutations in RAD52 and the BRCA1-BRCA2-PALB2 axis in human cancers

Altered cohesin dynamics and histone H3K9 modifications contribute to mitotic defects in thecbf11Δlipid metabolism mutant

Altered cohesin dynamics and H3K9 modifications contribute to mitotic defects in thecbf11Δlipid metabolism mutant

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