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Article ; Online: On the origin of the eukaryotic chromosome: the role of noncanonical DNA structures in telomere evolution.

Garavís, Miguel / González, Carlos / Villasante, Alfredo

2013 Volume 5, Issue 6, Page(s) 1142–1150

Abstract: The transition of an ancestral circular genome to multiple linear chromosomes was crucial for eukaryogenesis because it allowed rapid adaptive evolution through aneuploidy. Here, we propose that the ends of nascent linear chromosomes should have had a ... ...

Abstract	The transition of an ancestral circular genome to multiple linear chromosomes was crucial for eukaryogenesis because it allowed rapid adaptive evolution through aneuploidy. Here, we propose that the ends of nascent linear chromosomes should have had a dual function in chromosome end protection (capping) and chromosome segregation to give rise to the "proto-telomeres." Later on, proper centromeres evolved at subtelomeric regions. We also propose that both noncanonical structures based on guanine-guanine interactions and the end-protection proteins recruited by the emergent telomeric heterochromatin have been required for telomere maintenance through evolution. We further suggest that the origin of Drosophila telomeres may be reminiscent of how the first telomeres arose.
MeSH term(s)	Animals ; Centromere/genetics ; Chromosomes/genetics ; Evolution, Molecular ; G-Quadruplexes ; Humans ; Retroelements ; Telomerase/metabolism ; Telomere/genetics ; Telomere/metabolism
Chemical Substances	Retroelements ; Telomerase (EC 2.7.7.49)
Language	English
Publishing date	2013-05-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2495328-3
ISSN	1759-6653 ; 1759-6653
ISSN (online)	1759-6653
ISSN	1759-6653
DOI	10.1093/gbe/evt079
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Article ; Online: Centromeric Alpha-Satellite DNA Adopts Dimeric i-Motif Structures Capped by AT Hoogsteen Base Pairs.

Garavís, Miguel / Escaja, Núria / Gabelica, Valérie / Villasante, Alfredo / González, Carlos

Chemistry (Weinheim an der Bergstrasse, Germany)

2015 Volume 21, Issue 27, Page(s) 9816–9824

Abstract: Human centromeric alpha-satellite DNA is composed of tandem arrays of two types of 171 bp monomers; type A and type B. The differences between these types are concentrated in a 17 bp region of the monomer called the A/B box. Here, we have determined the ... ...

Abstract	Human centromeric alpha-satellite DNA is composed of tandem arrays of two types of 171 bp monomers; type A and type B. The differences between these types are concentrated in a 17 bp region of the monomer called the A/B box. Here, we have determined the solution structure of the C-rich strand of the two main variants of the human alpha-satellite A box. We show that, under acidic conditions, the C-rich strands of two A boxes self-recognize and form a head-to-tail dimeric i-motif stabilized by four intercalated hemi-protonated C:C(+) base pairs. Interestingly, the stack of C:C(+) base pairs is capped by T:T and Hoogsteen A:T base pairs. The two main variants of the A box adopt a similar three-dimensional structure, although the residues involved in the formation of the i-motif core are different in each case. Together with previous studies showing that the B box (known as the CENP-B box) also forms dimeric i-motif structures, our finding of this non-canonical structure in the A box shows that centromeric alpha satellites in all human chromosomes are able to form i-motifs, which consequently raises the possibility that these structures may play a role in the structural organization of the centromere.
MeSH term(s)	Base Pairing ; Base Sequence ; Centromere/chemistry ; DNA-Binding Proteins/metabolism ; Humans ; Intercalating Agents/chemistry ; Models, Molecular ; Nucleic Acid Conformation
Chemical Substances	DNA-Binding Proteins ; Intercalating Agents
Language	English
Publishing date	2015-06-26
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1478547-x
ISSN	1521-3765 ; 0947-6539
ISSN (online)	1521-3765
ISSN	0947-6539
DOI	10.1002/chem.201500448
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Article ; Online: Single-Stranded Condensation Stochastically Blocks G-Quadruplex Assembly in Human Telomeric RNA.

Gutiérrez, Irene / Garavís, Miguel / de Lorenzo, Sara / Villasante, Alfredo / González, Carlos / Arias-Gonzalez, J Ricardo

The journal of physical chemistry letters

2018 Volume 9, Issue 10, Page(s) 2498–2503

Abstract: TERRA is an RNA molecule transcribed from human subtelomeric regions toward chromosome ends potentially involved in regulation of heterochromatin stability, semiconservative replication, and telomerase inhibition, among others. TERRA contains tandem ... ...

Abstract	TERRA is an RNA molecule transcribed from human subtelomeric regions toward chromosome ends potentially involved in regulation of heterochromatin stability, semiconservative replication, and telomerase inhibition, among others. TERRA contains tandem repeats of the sequence GGGUUA, with a strong tendency to fold into a four-stranded arrangement known as a parallel G-quadruplex. Here, we demonstrate by using single-molecule force spectroscopy that this potential is limited by the inherent capacity of RNA to self-associate randomly and further condense into entropically more favorable structures. We stretched RNA constructions with more than four and less than eight hexanucleotide repeats, thus unable to form several G-quadruplexes in tandem, flanked by non-G-rich overhangs of random sequence by optical tweezers on a one by one basis. We found that condensed RNA stochastically blocks G-quadruplex folding pathways with a near 20% probability, a behavior that is not found in DNA analogous molecules.
MeSH term(s)	Base Sequence ; G-Quadruplexes ; Humans ; Nucleic Acid Denaturation ; Optical Tweezers ; RNA/chemistry ; Telomere/chemistry
Chemical Substances	RNA (63231-63-0)
Language	English
Publishing date	2018-05-17
Publishing country	United States
Document type	Journal Article
ISSN	1948-7185
ISSN (online)	1948-7185
DOI	10.1021/acs.jpclett.8b00722
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Article ; Online: The structure of an endogenous Drosophila centromere reveals the prevalence of tandemly repeated sequences able to form i-motifs.

Garavís, Miguel / Méndez-Lago, María / Gabelica, Valérie / Whitehead, Siobhan L / González, Carlos / Villasante, Alfredo

Scientific reports

2015 Volume 5, Page(s) 13307

Abstract: Centromeres are the chromosomal loci at which spindle microtubules attach to mediate chromosome segregation during mitosis and meiosis. In most eukaryotes, centromeres are made up of highly repetitive DNA sequences (satellite DNA) interspersed with ... ...

Abstract	Centromeres are the chromosomal loci at which spindle microtubules attach to mediate chromosome segregation during mitosis and meiosis. In most eukaryotes, centromeres are made up of highly repetitive DNA sequences (satellite DNA) interspersed with middle repetitive DNA sequences (transposable elements). Despite the efforts to establish complete genomic sequences of eukaryotic organisms, the so-called 'finished' genomes are not actually complete because the centromeres have not been assembled due to the intrinsic difficulties in constructing both physical maps and complete sequence assemblies of long stretches of tandemly repetitive DNA. Here we show the first molecular structure of an endogenous Drosophila centromere and the ability of the C-rich dodeca satellite strand to form dimeric i-motifs. The finding of i-motif structures in simple and complex centromeric satellite DNAs leads us to suggest that these centromeric sequences may have been selected not by their primary sequence but by their ability to form noncanonical secondary structures.
MeSH term(s)	Animals ; Base Pairing ; Base Sequence ; Centromere/genetics ; Chromosomes, Insect/genetics ; DNA, Satellite/genetics ; Dimerization ; Drosophila melanogaster/genetics ; Nucleotide Motifs/genetics ; Tandem Repeat Sequences/genetics
Chemical Substances	DNA, Satellite
Language	English
Publishing date	2015-08-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep13307
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Article ; Online: Health Survey in a Peruvian health system (ENSSA): design, methodology and general results.

Llanos, Renán Quispe / Ramírez, Rofilia Ramírez / Palacios, Martha Tizón / Flores, Claudio Flores / Borda-Olivas, Alfredo / Castillo, Roger Araujo / Guanira, Juan / Condor, Risof Solis / Villasante, Manuel Catacora / Hurtado-Roca, Yamilée

Revista de saude publica

2019 Volume 53, Page(s) 33

Abstract: Objective: To report the design, methodology and initial results of the National Socioeconomic Survey of Access to Health of the EsSalud Insured.: Results: There were interviews in 25,000 homes, surveying 79,874 people, of which 62,659 were ... ...

Abstract	Objective: To report the design, methodology and initial results of the National Socioeconomic Survey of Access to Health of the EsSalud Insured. Results: There were interviews in 25,000 homes, surveying 79,874 people, of which 62,659 were affiliated to EsSalud. The insured people are mainly males (50.6%) with a higher technical education level (39.7%). The insured population has mostly independent (95.0%) and own (68.1%) home. Only 34.5% of the insured practice some sport or physical exercise; 14.0% of the population suffers from a chronic disease; 3.5% have diabetes; and 7.1%, arterial hypertension. In the last three months, 35.4% of the members needed medical attention; of these, only 73.1% received health care and the remaining 10.9% were treated in pharmacies or non-formal health care services. Results: The 25,000 homes were interviewed, surveying 79,874 people, of which 62,659 were affiliated to EsSalud. The insured people are mainly males (50.6%) with a higher technical education level (39.7%). The insured population has mostly independent (95.0%) and own (68.1%) home. Only 34.5% of the insured practice some sport or physical exercise; 14.0% of the population suffers from a chronic disease; 3.5% have diabetes; and 7.1%, arterial hypertension. In the last three months, 35.4% of the members needed medical attention; of these, only 73.1% received health care and the remaining 10.9% were treated in pharmacies or non-formal health care services. Conclusions: This survey is the first performed in the population of EsSalud affiliates, applied at the national level, and has socio-economic and demographic data of the insured, their distribution, risk factors of health, prevalence of health problems and the degree of access to health services.
MeSH term(s)	Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Health Services Accessibility/statistics & numerical data ; Health Surveys ; Humans ; Infant ; Infant, Newborn ; Insurance, Health/statistics & numerical data ; Male ; Middle Aged ; National Health Programs ; Peru ; Socioeconomic Factors ; Young Adult
Language	Spanish
Publishing date	2019-04-01
Publishing country	Brazil
Document type	Journal Article
ZDB-ID	732179-x
ISSN	1518-8787 ; 0034-8910
ISSN (online)	1518-8787
ISSN	0034-8910
DOI	10.11606/S1518-8787.2019053001135
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Article ; Online: C6orf89 encodes three distinct HDAC enhancers that function in the nucleolus, the golgi and the midbody.

Lalioti, Vasiliki S / Vergarajauregui, Silvia / Villasante, Alfredo / Pulido, Diego / Sandoval, Ignacio V

Journal of cellular physiology

2013 Volume 228, Issue 9, Page(s) 1907–1921

Abstract: We report here that C6orf89, which encodes a protein that interacts with bombesin receptor subtype-3 and accelerates cell cycle progression and wound repair in human bronchial epithelial cells (Liu et al., 2011, PLoS ONE 6: e23072), encodes one soluble ... ...

Abstract	We report here that C6orf89, which encodes a protein that interacts with bombesin receptor subtype-3 and accelerates cell cycle progression and wound repair in human bronchial epithelial cells (Liu et al., 2011, PLoS ONE 6: e23072), encodes one soluble and two type II membrane proteins that function as histone deacetylases (HDAC) enhancers. Soluble 34/64sp is selectively targeted to the nucleolus and is retained in nucleolar organiser regions (NORs) in mitotic cells. Nucleolar 34/64sp is integrated into the ribosomal gene transcription machinery, colocalises and coimmunoprecipitates with the Pol I transcription factor UBF, and undergoes a dramatic relocalisation to the nucleolus upon the arrest of rDNA transcription, protein synthesis and PI3K/mTORC2 signalling. Membrane 42/116mp localises to the Golgi and the midbody, and its controlled ectopic expression provokes the disruption of the Golgi cisternae and hinders the separation of daughter cells and the completion of mitosis. The latter effect is also produced by the microinjection of an affinity-purified amfion antibody. The identification of C60rf89 as a gene that encodes three distinct proteins with the capacity to enhance the activity of histone deacetylases (HDACs) in the nucleolus, the Golgi and the midbody provides new information regarding the components of the acetylome and their capacity to interact with different functional groups in the cell.
MeSH term(s)	Cell Cycle/genetics ; Cell Nucleus/genetics ; Cell Nucleus/metabolism ; DNA, Ribosomal/genetics ; DNA, Ribosomal/metabolism ; DNA-Binding Proteins ; Enhancer Elements, Genetic ; Golgi Apparatus/genetics ; Golgi Apparatus/metabolism ; HeLa Cells ; Histone Deacetylases/genetics ; Histone Deacetylases/metabolism ; Humans ; Mitosis/genetics ; Nucleolus Organizer Region/genetics ; Nucleolus Organizer Region/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Proteins/genetics ; Proteins/metabolism ; Receptors, Bombesin/genetics ; Receptors, Bombesin/metabolism
Chemical Substances	C6orf89 protein, human ; DNA, Ribosomal ; DNA-Binding Proteins ; Proteins ; Receptors, Bombesin ; bombesin receptor subtype 3 ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Histone Deacetylases (EC 3.5.1.98)
Language	English
Publishing date	2013-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3116-1
ISSN	1097-4652 ; 0021-9541
ISSN (online)	1097-4652
ISSN	0021-9541
DOI	10.1002/jcp.24355
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Article ; Online: Curiously composite structures of a retrotransposon and a complex repeat associated with chromosome ends of Rhynchosciara americana (Diptera: Sciaridae).

Madalena, Christiane Rodriguez Gutierrez / Fernandes, Thiago / Villasante, Alfredo / Gorab, Eduardo

Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology

2010 Volume 18, Issue 5, Page(s) 587–598

Abstract: In Drosophila, telomere retrotransposons counterbalance the loss of telomeric DNA. The exceptional mechanism of telomere recovery characterized in Drosophila has not been found in lower dipterans (Nematocera). However, a retroelement resembling a ... ...

Abstract	In Drosophila, telomere retrotransposons counterbalance the loss of telomeric DNA. The exceptional mechanism of telomere recovery characterized in Drosophila has not been found in lower dipterans (Nematocera). However, a retroelement resembling a telomere transposon and termed "RaTART" has been described in the nematoceran Rhynchosciara americana. In this work, DNA and protein sequence analyses, DNA cloning, and chromosomal localization of probes obtained either by PCR or by screening a genomic library were carried out in order to examine additional features of this retroelement. The analyses performed raise the possibility that RaTART represents a genomic clone composed of distinct repetitive elements, one of which is likely to be responsible for its apparent enrichment at chromosome ends. RaTART sequence in addition allowed to assess a novel subtelomeric region of R. americana chromosomes that was analyzed in this work after subcloning a DNA fragment from a phage insert. It contains a complex repeat that is located in the vicinity of simple and complex tandem repeats characterized previously. Quantification data suggest that the copy number of the repeat is significantly lower than that observed for the ribosomal DNA in the salivary gland of R. americana. A short insertion of the RaTART was identified in the cloned segment, which hybridized preferentially to subtelomeres. Like RaTART, it displays truncated sequences related to distinct retrotransposons, one of which has a conceptual translation product with significant identity with an endonuclease from a lepidopteran retrotransposon. The composite structure of this DNA stretch probably reflects mobile element activity in the subtelomeric region analyzed in this work.
MeSH term(s)	3' Untranslated Regions ; Animals ; Base Sequence ; Chromosomes/chemistry ; Chromosomes/ultrastructure ; DNA/chemistry ; Diptera/genetics ; Molecular Sequence Data ; Repetitive Sequences, Nucleic Acid ; Retroelements ; Salivary Glands/chemistry ; Telomere/ultrastructure
Chemical Substances	3' Untranslated Regions ; Retroelements ; DNA (9007-49-2)
Language	English
Publishing date	2010-07-07
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1161632-5
ISSN	1573-6849 ; 0967-3849
ISSN (online)	1573-6849
ISSN	0967-3849
DOI	10.1007/s10577-010-9143-x
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Article ; Online: Health Survey in a Peruvian health system (ENSSA)

Renán Quispe Llanos / Rofilia Ramírez Ramírez / Martha Tizón Palacios / Claudio Flores Flores / Alfredo Borda-Olivas / Roger Araujo Castillo / Juan Guanira / Risof Solis Condor / Manuel Catacora Villasante / Yamilée Hurtado-Roca

Revista de Saúde Pública, Vol 53, Iss

design, methodology and general results

2019

Abstract: ABSTRACT OBJECTIVE To report the design, methodology and initial results of the National Socioeconomic Survey of Access to Health of the EsSalud Insured. RESULTS There were interviews in 25,000 homes, surveying 79,874 people, of which 62,659 were ... ...

Abstract	ABSTRACT OBJECTIVE To report the design, methodology and initial results of the National Socioeconomic Survey of Access to Health of the EsSalud Insured. RESULTS There were interviews in 25,000 homes, surveying 79,874 people, of which 62,659 were affiliated to EsSalud. The insured people are mainly males (50.6%) with a higher technical education level (39.7%). The insured population has mostly independent (95.0%) and own (68.1%) home. Only 34.5% of the insured practice some sport or physical exercise; 14.0% of the population suffers from a chronic disease; 3.5% have diabetes; and 7.1%, arterial hypertension. In the last three months, 35.4% of the members needed medical attention; of these, only 73.1% received health care and the remaining 10.9% were treated in pharmacies or non-formal health care services. RESULTS The 25,000 homes were interviewed, surveying 79,874 people, of which 62,659 were affiliated to EsSalud. The insured people are mainly males (50.6%) with a higher technical education level (39.7%). The insured population has mostly independent (95.0%) and own (68.1%) home. Only 34.5% of the insured practice some sport or physical exercise; 14.0% of the population suffers from a chronic disease; 3.5% have diabetes; and 7.1%, arterial hypertension. In the last three months, 35.4% of the members needed medical attention; of these, only 73.1% received health care and the remaining 10.9% were treated in pharmacies or non-formal health care services. CONCLUSIONS This survey is the first performed in the population of EsSalud affiliates, applied at the national level, and has socio-economic and demographic data of the insured, their distribution, risk factors of health, prevalence of health problems and the degree of access to health services.
Keywords	Encuestas Epidemiológicas ; métodos ; Encuesta Socioeconómica ; Muestreo ; Sistemas de Salud ; Public aspects of medicine ; RA1-1270
Subject code	360
Language	English
Publishing date	2019-04-01T00:00:00Z
Publisher	Universidade de São Paulo
Document type	Article ; Online
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Article ; Online: Neonatal meningitis: a multicenter study in Lima, Peru.

Guillén-Pinto, Daniel / Málaga-Espinoza, Bárbara / Ye-Tay, Joselyn / Rospigliosi-López, María Luz / Montenegro-Rivera, Andrea / Rivas, María / Stiglich, María Luisa / Villasante-Valera, Sonia / Lizama-Olaya, Olga / Tori, Alfredo / Cuba, Lizet / Florián, Luis / Vilchez-Fernández, Leidi / Eguiluz-Loaiza, Oscar / Dávila-Aliaga, Carmen Rosa / Medina-Alva, Pilar

Revista peruana de medicina experimental y salud publica

2020 Volume 37, Issue 2, Page(s) 210–219

Abstract: Objective: To determine the incidence and the clinical, bacteriological and cerebrospinal fluid characteristics of neonatal meningitis in Lima hospitals.: Materials and methods: An observational, multicenter study was conducted in six hospitals in ... ...

Title translation	Meningitis neonatal: estudio multicéntrico en Lima, Perú.
Abstract	Objective: To determine the incidence and the clinical, bacteriological and cerebrospinal fluid characteristics of neonatal meningitis in Lima hospitals. Materials and methods: An observational, multicenter study was conducted in six hospitals in the city of Lima during 1 year of epidemiological surveillance. Results: The cumulative hospital incidence was 1.4 cases per 1000 live births. A total of 53 cases of neonatal meningitis were included, 34% (18/53) were early and 66% (35/53) late. The associated maternal factors were meconium-stained amniotic fluid and urinary tract infection. Insufficient prenatal check-ups were found in 58.8% (30/51). The most associated neonatal factor was sepsis. The main symptoms were fever, irritability, hypoactivity and respiratory distress. Pleocytosis in cerebrospinal fluid (CSF) was significant, without predominance of polymorphonuclear lymphocytes (PMN), hypoglycorrhagia and proteinorrhagia. The most frequent pathogens isolated were Escherichia coli and Listeria monocytogenes. Conclusions: The hospital incidence of neonatal meningitis was 1.4 per 1000 live births, being ten times higher in preterm infants. Breathing difficulty was the most frequent symptom in the early stage, while fever and irritability in the late stage. CSF showed pleocytosis without predominance of PMN. The most frequent germs were Escherichia coli and Listeria monocytogenes. Ventriculitis and hydrocephalus were the most common neurological complications.
MeSH term(s)	Cities/epidemiology ; Hospitals ; Humans ; Incidence ; Infant, Newborn ; Infant, Newborn, Diseases/epidemiology ; Infant, Newborn, Diseases/microbiology ; Meningitis/epidemiology ; Meningitis/microbiology ; Peru/epidemiology
Keywords	covid19
Language	English
Publishing date	2020-08-28
Publishing country	Peru
Document type	Journal Article ; Multicenter Study ; Observational Study
ZDB-ID	2120092-0
ISSN	1726-4642 ; 1726-4642
ISSN (online)	1726-4642
ISSN	1726-4642
DOI	10.17843/rpmesp.2020.372.4772
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Article: Centromeres were derived from telomeres during the evolution of the eukaryotic chromosome.

Villasante, Alfredo / Abad, José P / Méndez-Lago, María

Proceedings of the National Academy of Sciences of the United States of America

2007 Volume 104, Issue 25, Page(s) 10542–10547

Abstract: The centromere is the DNA region of the eukaryotic chromosome that determines kinetochore formation and sister chromatid cohesion. Centromeres interact with spindle microtubules to ensure the segregation of chromatids during mitosis and of homologous ... ...

Abstract	The centromere is the DNA region of the eukaryotic chromosome that determines kinetochore formation and sister chromatid cohesion. Centromeres interact with spindle microtubules to ensure the segregation of chromatids during mitosis and of homologous chromosomes in meiosis. The origin of centromeres, therefore, is inseparable from the evolution of cytoskeletal components that distribute chromosomes to offspring cells. Although the origin of the nucleus has been debated, no explanation for the evolutionary appearance of centromeres is available. We propose an evolutionary scenario: The centromeres originated from telomeres. The breakage of the ancestral circular genophore activated the transposition of retroelements at DNA ends that allowed the formation of telomeres by a recombination-dependent replication mechanism. Afterward, the modification of the tubulin-based cytoskeleton that allowed specific subtelomeric repeats to be recognized as new cargo gave rise to the first centromere. This switch from actin-based genophore partition to a tubulin-based mechanism generated a transition period during which both types of cytoskeleton contributed to fidelity of chromosome segregation. During the transition, pseudodicentric chromosomes increased the tendency toward chromosomal breakage and instability. This instability generated multiple telocentric chromosomes that eventually evolved into metacentric or holocentric chromosomes.
MeSH term(s)	Biological Evolution ; Centromere/genetics ; Chromosomes/genetics ; Eukaryotic Cells/cytology ; Models, Genetic ; Telomere/genetics
Language	English
Publishing date	2007-06-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.0703808104
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