Integrating high-throughput analysis to create an atlas of replication origins in Trypanosoma cruzi in the context of genome structure and variability.

Autor:	Vitarelli MdO; Cell Cycle Laboratory, Butantan Institute, Av. Vital Brazil, São Paulo, Brazil.; Center of Toxins, Immune Response and Cell Signaling (CeTICS), Butantan Institute, Av. Vital Brazil, São Paulo, Brazil., Franco TA; Cell Cycle Laboratory, Butantan Institute, Av. Vital Brazil, São Paulo, Brazil., Pires DdS; Cell Cycle Laboratory, Butantan Institute, Av. Vital Brazil, São Paulo, Brazil., Lima ARJ; Center of Scientific Division, Butantan Institute, Av. Vital Brazil, São Paulo, Brazil., Viala VL; Biochemistry Laboratory, Butantan Institute, Av. Vital Brazil, São Paulo, Brazil., Kraus AJ; Division of Experimental Parasitology, Faculty of Veterinary Medicine, Ludwig-Maximilians-Universität in Munich, Planegg-Martinsried, Germany.; Biomedical Center, Division of Physiological Chemistry, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich, Planegg-Martinsried, Germany., de Azevedo IdLMJ; Applied Toxinology Laboratory, Butantan Institute, Av. Vital Brazil, São Paulo, Brazil., da Cunha JPC; Cell Cycle Laboratory, Butantan Institute, Av. Vital Brazil, São Paulo, Brazil.; Center of Toxins, Immune Response and Cell Signaling (CeTICS), Butantan Institute, Av. Vital Brazil, São Paulo, Brazil., Elias MC; Cell Cycle Laboratory, Butantan Institute, Av. Vital Brazil, São Paulo, Brazil.; Center of Toxins, Immune Response and Cell Signaling (CeTICS), Butantan Institute, Av. Vital Brazil, São Paulo, Brazil.
Jazyk:	angličtina
Zdroj:	MBio [mBio] 2024 Apr 10; Vol. 15 (4), pp. e0031924. Date of Electronic Publication: 2024 Mar 05.
DOI:	10.1128/mbio.00319-24
Abstrakt:	Trypanosoma cruzi is the etiologic agent of the most prevalent human parasitic disease in Latin America, Chagas disease. Its genome is rich in multigenic families that code for virulent antigens and are present in the rapidly evolving genomic compartment named Disruptive. DNA replication is a meticulous biological process in which flaws can generate mutations and changes in chromosomal and gene copy numbers. Here, integrating high-throughput and single-molecule analyses, we were able to identify Predominant, Flexible, and Dormant Orc1Cdc6-dependent origins as well as Orc1Cdc6-independent origins. Orc1Cdc6-dependent origins were found in multigenic family loci, while independent origins were found in the Core compartment that contains conserved and hypothetical protein-coding genes, in addition to multigenic families. In addition, we found that Orc1Cdc6 density is related to the firing of origins and that Orc1Cdc6-binding sites within fired origins are depleted of a specific class of nucleosomes that we previously categorized as dynamic. Together, these data suggest that Orc1Cdc6-dependent origins may contribute to the rapid evolution of the Disruptive compartment and, therefore, to the success of T. cruzi infection and that the local epigenome landscape is also involved in this process.IMPORTANCE Trypanosoma cruzi , responsible for Chagas disease, affects millions globally, particularly in Latin America. Lack of vaccine or treatment underscores the need for research. Parasite's genome, with virulent antigen-coding multigenic families, resides in the rapidly evolving Disruptive compartment. Study sheds light on the parasite's dynamic DNA replication, discussing the evolution of the Disruptive compartment. Therefore, the findings represent a significant stride in comprehending T. cruzi 's biology and the molecular bases that contribute to the success of infection caused by this parasite. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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