The Polycomb Group (PcG) system controls developmental transitions and cell states across species. Two main PcG complexes, Polycomb Repressive Complexes 1 and 2 (PRC1, PRC2), regulate transcription and form epigenetic memory through chromatin. Polyhomeotic (Ph) is an essential PRC1 subunit that has received relatively little attention, perhaps because it is not implicated in either depositing or recognizing histone post-translational modifications (PTMs). Instead, Ph regulates chromatin architecture through its hallmark polymerizing sterile alpha motif (SAM). Here we review the biochemistry and function of Ph and mammalian polyhomeotic-like proteins (PHCs). We describe the role of SAM polymerization and evidence for essential polymerization-independent SAM functions. The evolutionary origins of Ph and possible co-evolution of disordered and ordered regions to maintain but modify Ph function are considered. Finally, we draw parallels between SAM function in animals and a recently discovered polymerization activity in a plant PcG protein that may reflect convergent evolution.
Telomeres in epithelial tumors are maintained by telomerase; however, in the MDA-MB-231 breast cancer cell line, treated by doxorubicin (DOX), we found a transient suppression of the telomerase (TERT) before cell growth resumed. Accumulation of cells in late-S-G2/M, mitotic slippage, octaploidy, and decrease of lamin B1 (LMNB1) coincided with this response. The telomere clustering and ALT-like process marked by the telomere shelterin (TRF2) colocalised in PML bodies with DNA DSBs (γH2AX) and recombinase RAD51 were observed in 11-12% of cells. They were preset by arrays of PML-bodies juxta-colocalized with the foci of meiotic prophase proteins SPO11 and DMC1. On the 3rd week, the cells de-polyploidised and returned to the normal cycle, telomerase, and mitosis. ALT-like bodies were also found in BRAFV600E-SK-MEL-28 DOX-treated melanoma cells. However, after sublethal doses of DOX, the formation of PML dimeric rods flanked and tandemly joined by misrepaired TRF2/γH2AX foci occured. Such PML tracts, circumventing cell nuclei undergoing MOS-microtubule-driven rotation, interacted with peripheral chromatin and intermitted with LMNB1 fragments. Furthermore, LMNB1 massively left the nuclear periphery, forming intranuclear flows, and/or convoluted into large peri-nucleolar PML bodies. We interpret our observations as the attempts by damaged, senescing cancer cells to use several mechanisms exploiting PML isoforms and meiotic proteins for telomere repair.
Aging leads to a progressive loss of muscle mass and strength, termed sarcopenia, which is accelerated by inactivity and exacerbated by intrinsic cellular and molecular dysfunctions within the muscle fiber. Central to these changes is mechanotransduction, the process by which mechanical stimuli are converted into biochemical cues critical for protein synthesis, cytoskeletal remodeling, calcium signaling, and metabolism. Recent evidence highlights the nucleus as a key mechanosensory organelle in skeletal muscle. Forces transmitted from the extracellular matrix (ECM) through the cytoskeleton reach the nuclear envelope, where the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex and nuclear lamina convert physical stress into gene-regulatory events. Aging may alter these structures, producing changes in nuclear morphology, decreased stiffness, envelope fragility, and compromised transcriptional control. This review examines how the ECM, cytoskeleton, LINC complex, and nuclear lamina change in aged skeletal muscle, proposing that impaired nuclear mechanosignaling contributes to muscle fiber dysfunction during physiological aging.
Cuscuta janarthanamii Kolte, A. Deshp. Kambale, a recently described species, has been investigated for its chromosomal behaviour. This study reveals the presence of holocentric chromosomes and inverted meiosis in the species. This behaviour was confirmed with four distinct observations, namely the presence of an additional supernumerary chromosome during meiotic metaphase, parallel alignment of chromosomes to the equatorial plate, their movement in the same orientation towards poles and formation of bivalents of non-sister chromatids during meiotic anaphase-1. Collectively, these observations confirm that C. janarthanamii undergoes inverted meiosis, a phenomenon that may be linked to the adaptation of the species under environmental stress conditions. This article aligns with SDG 15 (Life on Land) of the UN Agenda for Sustainable Development.
Natural selection shapes the genome by favoring beneficial mutations, leading to selective sweeps through the hitchhiking effect. Identification of such sweeps provides valuable insights into genomic regions influencing adaptation and economically important traits. The present study was aimed to characterize hard and soft selective sweeps in Karan Fries (KF) cattle developed from crossing Holstein Friesian (HF) and Tharparkar (TH). A haplotype frequency spectrum-based approach using the T-statistics was employed to detect selective sweep signatures across the genome. KF exhibited a markedly higher number of hard sweeps (491) compared to HF (183) and TH (136), whereas the number of soft sweeps was comparable among the three breeds. The elevated hard sweep count in KF reflects rapid fixation of novel allelic combinations generated by Bos taurus and Bos indicus admixture under nine generations of intense artificial selection, producing a functionally heterogeneous hub-gene network spanning reproductive (GAS8), genome-maintenance (EXO1, ERCC1), and immune-regulatory (DBNDD1, DEF8) axes rather than converging on a single pathway as in the parental breeds. HF hard sweep hub genes (POLR2E, RPL19, EIF4A3) converged on ribosome biogenesis supporting lactational protein synthesis, while TH hub genes (GABRA4, GABRA5, GABRB1, GABRB3, GABRG3, IFNAR1) reflected tropical neurological and reproductive adaptation. Soft sweep hub genes across breeds converged on ribosomal and mitochondrial ribosomal proteins (KF: MED1, MRPL16, MRPL22; HF: RACK1, RPL27A, MRPS11; TH: MRPL1, MRPS12, MRPL24), indicating shared polygenic selection on translational efficiency. QTL analysis identified milk production as the dominant trait category. These findings offer candidate loci for customized genomic selection panels supporting sustainable tropical dairy production. This article aligns with SDG 2 (Zero Hunger) of the UN Agenda for Sustainable Development.
