DNA binding activity studies and computational approach of mutant SRY in patients with 46, XY complete pure gonadal dysgenesis

Irene Sánchez-Moreno, Patricia Canto, Patricia Munguía, Mario Bermúdez de León, Bulmaro Cisneros, Felipe Vilchis, Edgardo Reyes, Juan Pablo Méndez

Resultado de la investigación

7 Citas (Scopus)

Resumen

Mutations of SRY are the cause of 46,XY complete pure gonadal dysgenesis (PGD) in 10-15% of patients. In this study, DNA was isolated and sequenced from blood leukocytes and from paraffin-embedded gonadal tissue in five patients with 46,XY complete PGD. DNA binding capability was analyzed by three different methods. The structure of the full length SRY and its mutant proteins was carried out using a protein molecular model. DNA analysis revealed two mutations and one synonymous polymorphism: in patient #4 a Y96C mutation, and a E156 polymorphism; in patient #5 a S143G mosaic mutation limited to gonadal tissue. We demonstrated, by all methods used, that both mutant proteins reduced SRY DNA binding activity. The three-dimensional structure of SRY suggested that besides the HMG box, the carboxy-terminal region of SRY interacts with DNA. In conclusion, we identified two SRY mutations and a polymorphism in two patients with 46,XY complete PGD, demonstrating the importance of the carboxy-terminal region of SRY in DNA binding activity. © 2008 Elsevier Ireland Ltd. All rights reserved.
Idioma originalEnglish
Páginas (desde-hasta)212-218
Número de páginas7
PublicaciónMolecular and Cellular Endocrinology
DOI
EstadoPublished - 27 feb 2009
Publicado de forma externa

Huella dactilar

46,XY Gonadal Dysgenesis
DNA
Polymorphism
Mutation
Mutant Proteins
Tissue
Molecular Models
Ireland
Paraffin
Leukocytes
Blood

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Citar esto

Sánchez-Moreno, Irene ; Canto, Patricia ; Munguía, Patricia ; de León, Mario Bermúdez ; Cisneros, Bulmaro ; Vilchis, Felipe ; Reyes, Edgardo ; Méndez, Juan Pablo. / DNA binding activity studies and computational approach of mutant SRY in patients with 46, XY complete pure gonadal dysgenesis. En: Molecular and Cellular Endocrinology. 2009 ; pp. 212-218.
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title = "DNA binding activity studies and computational approach of mutant SRY in patients with 46, XY complete pure gonadal dysgenesis",
abstract = "Mutations of SRY are the cause of 46,XY complete pure gonadal dysgenesis (PGD) in 10-15{\%} of patients. In this study, DNA was isolated and sequenced from blood leukocytes and from paraffin-embedded gonadal tissue in five patients with 46,XY complete PGD. DNA binding capability was analyzed by three different methods. The structure of the full length SRY and its mutant proteins was carried out using a protein molecular model. DNA analysis revealed two mutations and one synonymous polymorphism: in patient #4 a Y96C mutation, and a E156 polymorphism; in patient #5 a S143G mosaic mutation limited to gonadal tissue. We demonstrated, by all methods used, that both mutant proteins reduced SRY DNA binding activity. The three-dimensional structure of SRY suggested that besides the HMG box, the carboxy-terminal region of SRY interacts with DNA. In conclusion, we identified two SRY mutations and a polymorphism in two patients with 46,XY complete PGD, demonstrating the importance of the carboxy-terminal region of SRY in DNA binding activity. {\circledC} 2008 Elsevier Ireland Ltd. All rights reserved.",
author = "Irene S{\'a}nchez-Moreno and Patricia Canto and Patricia Mungu{\'i}a and {de Le{\'o}n}, {Mario Berm{\'u}dez} and Bulmaro Cisneros and Felipe Vilchis and Edgardo Reyes and M{\'e}ndez, {Juan Pablo}",
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DNA binding activity studies and computational approach of mutant SRY in patients with 46, XY complete pure gonadal dysgenesis. / Sánchez-Moreno, Irene; Canto, Patricia; Munguía, Patricia; de León, Mario Bermúdez; Cisneros, Bulmaro; Vilchis, Felipe; Reyes, Edgardo; Méndez, Juan Pablo.

En: Molecular and Cellular Endocrinology, 27.02.2009, p. 212-218.

Resultado de la investigación

TY - JOUR

T1 - DNA binding activity studies and computational approach of mutant SRY in patients with 46, XY complete pure gonadal dysgenesis

AU - Sánchez-Moreno, Irene

AU - Canto, Patricia

AU - Munguía, Patricia

AU - de León, Mario Bermúdez

AU - Cisneros, Bulmaro

AU - Vilchis, Felipe

AU - Reyes, Edgardo

AU - Méndez, Juan Pablo

PY - 2009/2/27

Y1 - 2009/2/27

N2 - Mutations of SRY are the cause of 46,XY complete pure gonadal dysgenesis (PGD) in 10-15% of patients. In this study, DNA was isolated and sequenced from blood leukocytes and from paraffin-embedded gonadal tissue in five patients with 46,XY complete PGD. DNA binding capability was analyzed by three different methods. The structure of the full length SRY and its mutant proteins was carried out using a protein molecular model. DNA analysis revealed two mutations and one synonymous polymorphism: in patient #4 a Y96C mutation, and a E156 polymorphism; in patient #5 a S143G mosaic mutation limited to gonadal tissue. We demonstrated, by all methods used, that both mutant proteins reduced SRY DNA binding activity. The three-dimensional structure of SRY suggested that besides the HMG box, the carboxy-terminal region of SRY interacts with DNA. In conclusion, we identified two SRY mutations and a polymorphism in two patients with 46,XY complete PGD, demonstrating the importance of the carboxy-terminal region of SRY in DNA binding activity. © 2008 Elsevier Ireland Ltd. All rights reserved.

AB - Mutations of SRY are the cause of 46,XY complete pure gonadal dysgenesis (PGD) in 10-15% of patients. In this study, DNA was isolated and sequenced from blood leukocytes and from paraffin-embedded gonadal tissue in five patients with 46,XY complete PGD. DNA binding capability was analyzed by three different methods. The structure of the full length SRY and its mutant proteins was carried out using a protein molecular model. DNA analysis revealed two mutations and one synonymous polymorphism: in patient #4 a Y96C mutation, and a E156 polymorphism; in patient #5 a S143G mosaic mutation limited to gonadal tissue. We demonstrated, by all methods used, that both mutant proteins reduced SRY DNA binding activity. The three-dimensional structure of SRY suggested that besides the HMG box, the carboxy-terminal region of SRY interacts with DNA. In conclusion, we identified two SRY mutations and a polymorphism in two patients with 46,XY complete PGD, demonstrating the importance of the carboxy-terminal region of SRY in DNA binding activity. © 2008 Elsevier Ireland Ltd. All rights reserved.

U2 - 10.1016/j.mce.2008.10.012

DO - 10.1016/j.mce.2008.10.012

M3 - Article

SP - 212

EP - 218

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

SN - 0303-7207

ER -