Poly(ADP‐ribose) polymerase‐1 (PARP‐1) regulates developmental morphogenesis and chemotaxis in <i>Dictyostelium discoideum</i>

Jubin, Tina; Kadam, Ashlesha; Begum, Rasheedunnisa

doi:10.1111/boc.201800056

Cited by 6 publications

(2 citation statements)

References 63 publications

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“…PARP homologues are present in species from all major eukaryotic kingdoms (53). It was demonstrated that PARPs are essential for embryonic development in a variety of multi-cellular organisms, including mice, Drosophila, and fungi (20,(54)(55)(56). As noted above, the appearance of the PARP family proteins during the evolution of eukaryotes is possibly related to large sizes and chromatin organisation of their genomes.…”

Section: Roles Of Parp1 and Dna Supercoiling In The Chromatin Organismentioning

confidence: 94%

Mechanistic insight into the role of Poly(ADP-ribosyl)ation in DNA topology modulation and response to DNA damage

2019

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Genotoxic stress generates single- and double-strand DNA breaks either through direct damage by reactive oxygen species or as intermediates of DNA repair. Failure to detect and repair DNA strand breaks leads to deleterious consequences such as chromosomal aberrations, genomic instability and cell death. DNA strand breaks disrupt the superhelical state of cellular DNA, which further disturbs the chromatin architecture and gene activity regulation. Proteins from the poly(ADP-ribose) polymerase (PARP) family, such as PARP1 and PARP2, use NAD+ as a substrate to catalyse the synthesis of polymeric chains consisting of ADP-ribose units covalently attached to an acceptor molecule. PARP1 and PARP2 are regarded as DNA damage sensors that, upon activation by strand breaks, poly(ADP-ribosyl)ate themselves and nuclear acceptor proteins. Noteworthy, the regularly branched structure of poly(ADP-ribose) polymer suggests that the mechanism of its synthesis may involve circular movement of PARP1 around the DNA helix, with a branching point in PAR corresponding to one complete 360° turn. We propose that PARP1 stays bound to a DNA strand break end, but rotates around the helix displaced by the growing poly(ADP-ribose) chain, and that this rotation could introduce positive supercoils into damaged chromosomal DNA. This topology modulation would enable nucleosome displacement and chromatin decondensation around the lesion site, facilitating the access of DNA repair proteins or transcription factors. PARP1-mediated DNA supercoiling can be transmitted over long distances, resulting in changes in the high-order chromatin structures. The available structures of PARP1 are consistent with the strand break-induced PAR synthesis as a driving force for PARP1 rotation around the DNA axis.

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Section: Roles Of Parp1 and Dna Supercoiling In The Chromatin Organismentioning

confidence: 94%

Mechanistic insight into the role of Poly(ADP-ribosyl)ation in DNA topology modulation and response to DNA damage

2019

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“…In addition, ADPRT1A knockout (ADPRT1A -) cells also exhibited defective chemotaxis and delay in development, affected prestalk and prespore (ecmA and d19, respectively) gene expression and altered the transcript profile of cAMP production and signalling. However, the exogenous cAMP pulses could rescue these defects in the ADPRT1A - (Jubin et al, 2019a). Altered PARP-1 levels in fungi have been shown to manifest defective development and decreased life span (Kothe et al, 2010).…”

Section: Multicellular Development and Morphogenesismentioning

confidence: 99%

Glimpses of Dictyostelid research in India

Begum¹,

Saran²

2020

Int. J. Dev. Biol.

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Simple organisms are preferred for understanding the molecular and cellular function(s) of complex processes. Dictyostelium discoideum is a lower eukaryote, a protist and a cellular slime mould, which has been in recent times used for various studies such as cell differentiation, development, cell death, stress responses etc. It is a soil amoeba (unicellular) that undertakes a remarkable, facultative shift to multicellularity when exposed to starvation and requires signal pathways that result in alteration of gene expression and finally show cell differentiation. The amoebae aggregate, differentiate and form fruiting bodies with two terminally differentiated cells: the dead stalk (non-viable) and dormant spores (viable). In India, starting from the isolation of Dictyostelium species to morphogenesis, cell signalling and social evolution has been studied with many more new research additions. Advances in molecular genetics make Dictyostelium an attractive model system to study cell biology, biochemistry, signal transduction and many more.

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