Non-tumor cells from an MSH2-null individual show altered cell cycle effects post-UVB

Narine, Kelly A.D.; Felton, Kathleen; Parker, Arabesque; Tron, Victor A.; Andrew, Susan E.

doi:10.3892/or.18.6.1403

Cited by 8 publications

(7 citation statements)

References 47 publications

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“…DNA MMR is involved in maintaining DNA integrity in all organisms and its proteins have been highly conserved during evolution (Surtees et al, 2004). A defective MMR is the cause of Lynch Syndrome in humans, which makes them more likely to develop certain types of cancer (Nicolaides et al, 1998; Modrich, 2006; Narine et al, 2007; Seifert et al, 2008). Plants being sessile, have to cope with external and endogenous mutagens that cause replication errors (chemicals such as heavy metals, alkylating agents or reactive oxygen species, ROS and solar UV-B radiation etc.).…”

Section: Discussionmentioning

confidence: 99%

New Phenotypes of Potato Co-induced by Mismatch Repair Deficiency and Somatic Hybridization

et al. 2019

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As plants are sessile they need a very efficient system for repairing damage done by external or internal mutagens to their DNA. Mismatch repair (MMR) is one of the systems that maintain genome integrity and prevent homeologous recombination. In all eukaryotes mismatches are recognized by evolutionary conserved MSH proteins often acting as heterodimers, the constant component of which is MSH2. Changes affecting the function of MSH2 gene may induce a ‘mutator’ phenotype and microsatellite instability (MSI), as is demonstrated in MSH2 knock-out and silenced lines of Arabidopsis thaliana. The goal of this study was to screen for ‘mutator’ phenotypes in somatic hybrids between potato cvs. ‘Delikat’ and ‘Désirée’ and MMR deficient Solanum chacoense transformed using antisense (AS) or dominant negative mutant (DN) AtMSH2 genes. The results demonstrate that first generation fusion hybrids have a range of morphological abnormalities caused by uniparental MMR deficiency; these mutant phenotypes include: dwarf or gigantic plants; bushiness; curled, small, large or abnormal leaves; a deterioration in chloroplast structure; small deep-purple tubers and early dehiscent flowers. Forty percent of the viable somatic hybrids planted in a greenhouse, (10 out of 25 genotypes) had mutant phenotypes accompanied by MSI. The majority of the hybrids with ‘mutator’ phenotypes cultured on media containing kanamycin developed roots so sustaining the presence of selectable marker gene nptII, from the initial constructs. Here for the first time, MMR deficiency combined with somatic hybridization, are used to induce new phenotypes in plants, which supports the role of MMR deficiency in increasing introgressions between two related species.

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Section: Discussionmentioning

confidence: 99%

New Phenotypes of Potato Co-induced by Mismatch Repair Deficiency and Somatic Hybridization

et al. 2019

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“…Experiments conducted in msh2−/− nontumor human lymphoblastoid cell lines have shown that the MMR system promotes G2/M arrest after UV-B induced DNA damage, and that a deficiency in MSH2 leads to a decrease in the induction of G2/M cell cycle checkpoint following this type of radiation. MSH2 proficient human lymphoblastoid cell lines cells also increase cell cycle checkpoint proteins levels such as CHK1, CDC25C, and CDC2, when compared with MSH2-deficient cells, after UV-B radiation treatment [ 29 ]. These proteins, when phosphorylated at specific amino acidic residues (Ser345, Ser216, Tyr15, and Thr14), regulate cell cycle control and inhibit cells from dividing until the DNA alterations are corrected, in accordance with MMR system's capacity to induce arrest in proliferative cells [ 30 , 31 ].…”

Section: Dna Mmr System and Cell Cycle Arrest Processmentioning

confidence: 99%

DNA Mismatch Repair System: Repercussions in Cellular Homeostasis and Relationship with Aging

Conde-Pérezprina

León-Galván

Königsberg

2012

Oxidative Medicine and Cellular Longevity

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The mechanisms that concern DNA repair have been studied in the last years due to their consequences in cellular homeostasis. The diverse and damaging stimuli that affect DNA integrity, such as changes in the genetic sequence and modifications in gene expression, can disrupt the steady state of the cell and have serious repercussions to pathways that regulate apoptosis, senescence, and cancer. These altered pathways not only modify cellular and organism longevity, but quality of life (“health-span”). The DNA mismatch repair system (MMR) is highly conserved between species; its role is paramount in the preservation of DNA integrity, placing it as a necessary focal point in the study of pathways that prolong lifespan, aging, and disease. Here, we review different insights concerning the malfunction or absence of the DNA-MMR and its impact on cellular homeostasis. In particular, we will focus on DNA-MMR mechanisms regulated by known repair proteins MSH2, MSH6, PMS2, and MHL1, among others.

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“…In mammalian cells, the contribution of the MMR pathway to the UVB-induced DNA damage is well established (Narine et al ., 2007; Seifert et al ., 2008). Similarly, Arabidopsis MSH2 T-DNA insertion lines show higher levels of Cyclobutane Pyrimidine Dimer (CPD) on exposure to UV-B (Lario et al ., 2011, 2015).…”

Section: Resultsmentioning

confidence: 99%

MutS-Homolog2silencing generates tetraploid meiocytes in tomato (Solanum lycopersicum)

Sarma

Pandey

Ravi

et al. 2017

Preprint

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SUMMARYMSH2 is the core protein of MutS-homolog family involved in recognition and repair of the errors in the DNA. While other members of MutS-homolog family reportedly regulate mitochondrial stability, meiosis, and fertility, MSH2 is believed to participate mainly in mismatch repair. The search for polymorphism in MSH2 sequence in tomato accessions revealed both synonymous and nonsynonymous SNPs; however, SIFT algorithm predicted that none of the SNPs influenced MSH2 protein function. The silencing of MSH2 gene expression by RNAi led to phenotypic abnormalities in highly-silenced lines, particularly in the stamens with highly reduced pollen formation. MSH2 silencing exacerbated formation of UV-B induced thymine dimers and blocked light-induced repair of the dimers. The MSH2 silencing also affected the progression of male meiosis to a varying degree with either halt of meiosis at zygotene stage or formation of diploid tetrads. The immunostaining of male meiocytes with centromere localized CENPC (Centromere protein C) protein antibody showed the presence of 48 univalent along with 24 bivalent chromosomes suggesting abnormal tetraploid meiosis. The mitotic cells of root tips of silenced lines showed diploid nuclei but lacked intervening cell plates leading to cells with syncytial nuclei. Thus we speculate that tetraploid pollen mother cells may have arisen due to the fusion of syncytial nuclei before the onset of meiosis. It is likely that in addition to Mismatch repair (MMR), MSH2 may have an additional role in regulating ploidy stability.

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Non-tumor cells from an MSH2-null individual show altered cell cycle effects post-UVB

Cited by 8 publications

References 47 publications

New Phenotypes of Potato Co-induced by Mismatch Repair Deficiency and Somatic Hybridization

New Phenotypes of Potato Co-induced by Mismatch Repair Deficiency and Somatic Hybridization

DNA Mismatch Repair System: Repercussions in Cellular Homeostasis and Relationship with Aging

MutS-Homolog2silencing generates tetraploid meiocytes in tomato (Solanum lycopersicum)

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