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Biology subjects

Tsaridou, S.

Publications and source records attributed to Tsaridou, S..

2 recordsLinked to original sources

McIdas localizes at centrioles and controls centriole numbers through PLK4-dependent phosphorylation

The centriole duplication cycle must be tightly controlled and coordinated with the chromosome cycle. Aberrations in centriole biogenesis can lead to cancer, developmental disorders and ciliopathies. Here, we show that McIdas -previously implicated in cell cycle control and centriole amplification in multiciliated cells-is critical to maintain centriole numbers. Using expansion microscopy, we demonstrate that McIdas is present at the middle part of centrioles, where it exhibits a differential localization during the cell cycle. McIdas loss perturbs daughter centriole biogenesis and centrosomal SAS6 recruitment, whereas its overexpression induces centriole overduplication. Consistently, McIdas depletion reduces PLK4-induced centriole amplification. McIdas interacts with and is phosphorylated by PLK4 in multiple sites identified by mass spectrometry. Mutational analysis shows that McIdas phosphorylation is important for centriole number control. Overall, our results identify a novel, direct role of McIdas on centriole duplication that can link its previously characterized roles in the chromosome cycle and multiciliogenesis.

molecular biology↗

53BP1 mediated recruitment of RASSF1A at ribosomal DNA breaks facilitates local ATM signal amplification

DNA lesions occur across the genome and constitute a threat to cell viability; however, damage at specific genomic loci has a disproportionally greater impact on the overall genome stability. The ribosomal RNA gene repeats (rDNA) are emerging fragile sites due to repetitive nature, clustering and high transcriptional activity. Notably, recent progress in understanding how the rDNA damage response is organized has highlighted the key role of adaptor proteins in the response. Here we identify that the scaffold and tumor suppressor, RASSF1A is recruited at sites of damage and particularly enriched at rDNA breaks. Employing targeted nucleolar DNA damage, we find that RASSF1A recruitment requires ATM activity and depends on the 53BP1. At sites of damage RASSF1A facilitates local ATM signal establishment and rDNA break repair. RASSF1A silencing, a common epigenetic event during malignant transformation, results in persistent breaks, rDNA copy number alterations and decreased cell viability. Moreover, meta-analysis of a lung adenocarcinoma cohort showed that epigenetic silencing of the scaffold leads in rDNA copy number discrepancies. Overall, we present evidence that RASSF1A acts as a DNA repair factor and offer mechanistic insight in how the nucleolar DNA damage response is organized.

cell biology↗