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Multicopy subtelomeric genes underlie animal infectivity of divergent Cryptosporidium hominis subtypes.
Nat Commun
December 2024
State Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
The anthroponotic Cryptosporidium hominis differs from the zoonotic C. parvum in its lack of infectivity to animals, but several divergent subtypes have recently been found in nonhuman primates and equines. Here, we sequence 17 animal C.
View Article and Find Full Text PDFIdentification of modulators of the ALT pathway through a native FISH-based optical screen.
Cell Rep
December 2024
Laboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:
A significant portion of human cancers utilize a recombination-based pathway, alternative lengthening of telomeres (ALT), to extend telomeres. To gain further insights into this pathway, we developed a high-throughput imaging-based screen named TAILS (telomeric ALT in situ localization screen) to identify genes that either promote or inhibit ALT activity. Screening over 1,000 genes implicated in DNA transactions, TAILS reveals both well-established and putative ALT modulators.
View Article and Find Full Text PDFTranscription as a double-edged sword in genome maintenance.
FEBS Lett
December 2024
Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
Genome maintenance is essential for the integrity of the genetic blueprint, of which only a small fraction is transcribed in higher eukaryotes. DNA lesions occurring in the transcribed genome trigger transcription pausing and transcription-coupled DNA repair. There are two major transcription-coupled DNA repair pathways.
View Article and Find Full Text PDFMaintaining Telomeres without Telomerase in : Novel Mechanisms and Rapid Evolution to Save a Genus.
Cold Spring Harb Perspect Biol
December 2024
Department of Biology and Biotechnology, Sapienza University of Rome, 00185 Rome, Italy
Telomere maintenance is crucial for preventing the linear eukaryotic chromosome ends from being mistaken for DNA double-strand breaks, thereby avoiding chromosome fusions and the loss of genetic material. Unlike most eukaryotes that use telomerase for telomere maintenance, relies on retrotransposable elements-specifically , , and (collectively referred to as HTT)-which are regulated and precisely targeted to chromosome ends. telomere protection is mediated by a set of fast-evolving proteins, termed terminin, which bind to chromosome termini without sequence specificity, balancing DNA damage response factors to avoid erroneous repair mechanisms.
View Article and Find Full Text PDFTelAP2 links TelAP1 to the telomere complex in Trypanosoma brucei.
Sci Rep
December 2024
Quantitative Proteomics, Institute of Molecular Biology (IMB), 55128, Mainz, Germany.
The extracellular parasite Trypanosoma brucei evades the immune system of the mammalian host by periodically exchanging its variant surface glycoprotein (VSG) coat. Hereby, only one VSG gene is transcribed from one of 15 subtelomeric so-called bloodstream form expression sites (BES) at any given timepoint, while all other BESs are silenced. VSG gene expression is altered by homologous recombination using a large VSG gene repertoire or by a so-called in situ switch, which activates a previously silent BES.
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