PubMed · 7960931
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M Ghosh, A R Khape, B B Bannur. rDNA based pharmaceuticals (selected information).. https://pubmed.ncbi.nlm.nih.gov/7960931/
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The nucleolus is organized around actively transcribed ribosomal RNA genes (rDNA), where high RNA polymerase I (Pol I) activity creates intrinsic susceptibility to replication stress and DNA damage. Here, we identify the DNA translocase RAD54L as a critical regulator of the nucleolar DNA damage response (nDDR) to rDNA double-strand breaks (DSBs) and replication stress. We show that RAD54L localizes to the nucleolus under basal conditions and is recruited to nucleolar caps following CRISPR-Cas9-induced rDNA-DSBs to promote repair. RAD54L loss results in persistent RAD51 foci, increased nucleolar γH2AX, and micronuclei formation, indicating defective resolution of rDNA lesions and genome instability. Under baseline conditions and replication stress induced by the Pol I transcription inhibitor CX-5461, RAD54L limits the accumulation of ssDNA and coordinates nDDR signaling. We further show that rDNA-DSBs induce RNA polymerase II-dependent RNA-DNA hybrids (R-loops) at intergenic rDNA regions, which facilitate nucleolar reorganization and cap formation and repair factor recruitment. Together, these findings establish RAD54L as a key regulator that coordinates replication stress response and rDNA repair, maintaining rDNA stability and genome integrity.
Allopolyploid Spartina anglica C.E. Hubbard (2n = 120-124) has become recognized as a model system of recent allopolyploid speciation. It arose by interspecific hybridization between S. alterniflora (2n = 62) introduced from North America and the native European S. maritima (2n = 60) about 150 years ago. In addition, sterile first-generation homoploid hybrids S. × townsendii and S. × neyrautii (both 2n = 62) are still extant. In this study, we carried out a population-level study of epigenetic silencing of 35S rDNA loci, also known as nucleolar dominance. Using molecular, genomic, and cytogenetic methods, we analyzed 75 individuals of S. anglica (collected from 11 French populations and 5 UK populations), 34 individuals of S. × townsendii (3 populations, all from the UK), and 2 individuals of S. × neyrautii from the south of France. We observed strong transcriptional dominance of S. alterniflora-inherited rDNA in all hybrid and allopolyploid individuals. The dominant rDNA units were nearly devoid of methylation at CWG sites, in contrast to those of the silenced S. maritima-inherited rDNA (M-loci), which exhibited hypermethylation. At the DNA level, few (2%) S. anglica individuals have completely lost M-loci, indicating that rDNA diploidization proceeds extremely fast in Spartina, and such a process may be influenced by preceding epigenetic processes. We conclude that nucleolar dominance is already present in extant homoploid hybrid lineages and is largely maintained in S. anglica, with occasional partial relaxation.
The phylogenetic relationships of some angiosperm families have remained enigmatic despite broad phylogenetic analyses of rbcL sequences. One example is the aquatic family Podostemaceae, the relationships of which have long been controversial because of major morphological modifications associated with their aquatic habit. Podostemaceae have variously been associated with Piperaceae, Nepenthaceae, Polygonaceae, Caryophyllaceae, Scrophulariaceae, Rosaceae, Crassulaceae, and Saxifragaceae. Two recent analyses of rbcL sequences suggest a possible sister-group relationship of Podostemaceae to Crassulaceae (Saxifragales). However, the branch leading to Podostemaceae was long, and use of different outgroups resulted in alternative placements. We explored the phylogenetic relationships of Podostemaceae using 18S rDNA sequences and a combined rbcL + 18S rDNA matrix representing over 250 angiosperms. In analyses based on 18S rDNA data, Podostemaceae are not characterized by a long branch; the family consistently appears as part of a Malpighiales clade that also includes Malpighiaceae, Turneraceae, Passifloraceae, Salicaceae, Euphorbiaceae, Violaceae, Linaceae, Chrysobalanaceae, Trigoniaceae, Humiriaceae, and Ochnaceae. Phylogenetic analyses based on a combined 18S rDNA + rbcL data set (223 ingroup taxa) with basal angiosperms as the outgroup also suggest that Podostemaceae are part of a Malpighiales clade. These searches swapped to completion, and the shortest trees showed enhanced resolution and increased internal support compared to those based on 18S rDNA or rbcL alone. However, when Gnetales are used as the outgroup, Podostemaceae appear with members of the nitrogen fixing clade (e.g., Elaeagnaceae, Ulmaceae, Rhamnaceae, Cannabaceae, Moraceae, and Urticaceae). None of the relationships suggested here for Podostemaceae receives strong bootstrap support. Our analyses indicate that Podostemaceae are not closely allied with Crassulaceae or with other members of the Saxifragales clade; their closest relatives, although still uncertain, appear to lie elsewhere in the rosids.