Integrating plant and animal biology for the search of novel DNA damage biomarkers

Nikitaki, Zacharenia; Holá, Marcela; Donà, Mattia; Pavlopoulou, Athanasia; Michalopoulos, Ioannis; Angelis, Karel J.; Georgakilas, Alexandros G.; Macovei, Anca; Balestrazzi, Alma

doi:10.1016/j.mrrev.2018.01.001

Cited by 27 publications

(21 citation statements)

References 209 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To characterize repair defects of pprad51 , pprtel1 and ppsol we compared their capabilities to remove lesions as DSBs induced by radiomimetic bleomycin, small alkylation adducts induced by methyl methanesulfonate (MMS) and bulky DNA helix distortion by inducing pyrimidine photodimers and 6′‐4′‐photoproducts by UVC irradiation. These lesions represent blocks for DNA replication and are repaired or bypassed by various error‐free as well as error‐prone pathways (Holá et al ., ; Manova and Gruszka, ; Nikitaki et al ., ) The sensitivity of protonemata was tested by 1 h of acute treatment with genotoxin in a liquid medium, followed by explants subculture on Petri plates with the drug‐free medium to determine the ability of the tissue to recover. Explant growth after 3 weeks was monitored as a plant fresh weight rather than plant surface area (Kamisugi et al ., ) as their diameters versus explant mass substantially differed in studied lines (Figure ).…”

Section: Resultsmentioning

confidence: 99%

“…Upon replication stress imposed by deficiency of RTEL1 in A. thaliana , a replication checkpoint is activated that is controlled by a master regulator of the DNA damage response in plants, SOG1 (Suppressor Of Gamma1), with a characteristic NAC domain (Hu et al ., ). The response to DNA damage starts with a transient induction of general stress genes that is coincident with the sustained induction of DNA repair genes and is followed, after a short delay, by the repression of the cell‐cycle regulating genes (recently reviewed in Nikitaki et al ., ). SOG1 mutants suppress radiation‐induced arrest and proceed through the cell cycle unimpeded (Preuss and Britt, ; Adachi et al ., ).…”

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

Roles of RAD51 and RTEL1 in telomere and rDNA stability in Physcomitrella patens

et al. 2019

Self Cite

View full text Add to dashboard Cite

These authors contributed equally. SUMMARYTelomeres and ribosomal RNA genes (rDNA) are essential for cell survival and particularly sensitive to factors affecting genome stability. Here, we examine the role of RAD51 and its antagonist, RTEL1, in the moss Physcomitrella patens. In corresponding mutants, we analyse their sensitivity to DNA damage, the maintenance of telomeres and rDNA, and repair of double-stranded breaks (DSBs) induced by genotoxins with various modes of action. While the loss of RTEL1 results in rapid telomere shortening, concurrent loss of both RAD51 genes has no effect on telomere lengths. We further demonstrate here the linked arrangement of 5S and 45S rRNA genes in P. patens. The spacer between 5S and 18S rRNA genes, especially the region downstream from the transcription start site, shows conspicuous clustering of sites with a high propensity to form quadruplex (G4) structures. Copy numbers of 5S and 18S rDNA are reduced moderately in the pprtel1 mutant, and significantly in the double pprad51-1-2 mutant, with no progression during subsequent cultivation. While reductions in 45S rDNA copy numbers observed in pprtel1 and pprad51-1-2 plants apply also to 5S rDNA, changes in transcript levels are different for 45S and 5S rRNA, indicating their independent transcription by RNA polymerase I and III, respectively. The loss of SOL (Sog One-Like), a transcription factor regulating numerous genes involved in DSB repair, increases the rate of DSB repair in dividing as well as differentiated tissue, and through deactivation of G2/M cell-cycle checkpoint allows the cell-cycle progression manifested as a phenotype resistant to bleomycin.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Roles of RAD51 and RTEL1 in telomere and rDNA stability in Physcomitrella patens

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Despite the constantly improving image resolution offered by novel microscopy techniques, the fundamental limitation of DNA damage detection is defined by the number of DNA repair enzymes that can be simultaneously detected. Given that each DNA repair pathway utilizes dozens of proteins and the fact that in case of complex damage many pathways are simultaneously involved, an exhaustive observation should detect hundreds of different types of molecules (507 in Homo sapiens [156]). Up to now, the majority of relevant experiments detect up to three DNA repair enzymes simultaneously, which is a serious technical limitation that needs advancement in the future.…”

Section: The Persistent Weakness Of Complex Dna Damage Detectionmentioning

confidence: 99%

In Situ Detection of Complex DNA Damage Using Microscopy: A Rough Road Ahead

Nikitaki

Pariset

Sudar

et al. 2020

Cancers

Self Cite

View full text Add to dashboard Cite

Complexity of DNA damage is considered currently one if not the primary instigator of biological responses and determinant of short and long-term effects in organisms and their offspring. In this review, we focus on the detection of complex (clustered) DNA damage (CDD) induced for example by ionizing radiation (IR) and in some cases by high oxidative stress. We perform a short historical perspective in the field, emphasizing the microscopy-based techniques and methodologies for the detection of CDD at the cellular level. We extend this analysis on the pertaining methodology of surrogate protein markers of CDD (foci) colocalization and provide a unique synthesis of imaging parameters, software, and different types of microscopy used. Last but not least, we critically discuss the main advances and necessary future direction for the better detection of CDD, with important outcomes in biological and clinical setups.

show abstract

“…To maintain genome integrity, cells constantly monitor the status of DNA during cell cycle progression and arrest cell cycle immediately upon detection of DNA damage (De Schutter et al ., ). PCD is a faster alternative to remove damaged cells and to protect germlines in plant stem‐cell niches than cell cycle checkpoint activation and DNA repair mechanism (Fulcher and Sablowski, ; Nikitaki et al ., ).…”

Section: Introductionmentioning

confidence: 97%

“…These kinases activate a transcriptional regulator, p53, that controls components of the DDR including cell cycle arrest, DNA damage repair and apoptosis (Shieh et al ., ; Chen and Sanchez, ; Rozan and El‐Deiry, ; Lu et al ., ). Many DDR genes are regularly expressed and share the same eukaryotic ancestor in animals and plants (Sancar et al ., ; Nikitaki et al ., ). However, CHK1/2 and p53, the main signal transducers for the DDR in animals, do not exist in plants (Garcia et al ., ; Ricaud et al ., ).…”

Section: Introductionmentioning

confidence: 97%

SOG1‐dependent NAC103 modulates the DNA damage response as a transcriptional regulator in Arabidopsis

Ryu

Choi

et al. 2019

The Plant Journal

View full text Add to dashboard Cite

These authors contributed equally to this work. SUMMARYThe plant-specific transcription factor (TF) NAC103 was previously reported to modulate the unfolded protein response in Arabidopsis under endoplasmic reticulum (ER) stress. Alternatively, we report here that NAC103 is involved in downstream signaling of SOG1, a master regulator for expression of DNA damage response (DDR) genes induced by genotoxic stress. Arabidopsis NAC103 expression was strongly induced by genotoxic stress and nac103 mutants displayed substantial inhibition of DDR gene expression after gamma radiation or radiomimetic zeocin treatment. DDR phenotypes, such as true leaf inhibition, root cell death and root growth inhibition, were also suppressed significantly in the nac103 mutants, but to a lesser extent than in the sog1-1 mutant. By contrast, overexpression of NAC103 increased DDR gene expression without genotoxic stress and substantially rescued the phenotypic changes in the sog1-1 mutant after zeocin treatment. The putative promoters of some representative DDR genes, RAD51, PARP1, RPA1E, BRCA1 and At4g22960, were found to partly interact with NAC103. Together with the expected interaction of SOG1 with the promoter of NAC103, our study suggests that NAC103 is a putative SOG1-dependent transcriptional regulator of plant DDR genes, which are responsible for DDR phenotypes under genotoxic stress.

show abstract

Integrating plant and animal biology for the search of novel DNA damage biomarkers

Cited by 27 publications

References 209 publications

Roles of RAD51 and RTEL1 in telomere and rDNA stability in Physcomitrella patens

Roles of RAD51 and RTEL1 in telomere and rDNA stability in Physcomitrella patens

In Situ Detection of Complex DNA Damage Using Microscopy: A Rough Road Ahead

SOG1‐dependent NAC103 modulates the DNA damage response as a transcriptional regulator in Arabidopsis

Contact Info

Product

Resources

About