Structural studies with mammalian importin-alpha and nuclear localization sequences (NLS) from proteins involved in DNA repair

• Grant number: 11/09905-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: September 01, 2011
• End date: July 31, 2015
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Marcos Roberto de Mattos Fontes
• Grantee: Andréa Coelho de Barros
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The stability and integrity of the genetic material are essential for the maintenance and continuation of life. The human genome, comprising three billion base pairs coding for 30.000 - 40.000 genes, is constantly attacked by endogenous reactive metabolites, therapeutic drugs and a plethora of environmental mutagens that impact its integrity. Thus it is obvious that the stability of the genome must be under continuous surveillance. This is accomplished by DNA repair mechanisms, which were developed to remove or tolerate injuries and mistakes in DNA. In the DNA repair mechanisms available in the organisms, they can be divided in: i) base excision repair (BER), ii) nucleotide excision repair (NER), iii) mismatch repair (MMR) and iv) DNA repair by non-homologous end joining (NHEJ). To an adequate operation of these mechanisms, it is evident the importance of the interaction between proteins responsible for the function of DNA repair, as well as the regulation for nuclear import is essential for the correct localization of the proteins responsible for the mentioned mechanisms. In the group of the mechanisms responsible for nuclear import regulation, the classical pathway composed by Importin-±/² heterodimer is one of the major mechanisms of transport. Some DNA repair proteins seem to interact only with certain isoforms of Importin-± (Imp±), indicating an additional regulation of the repair process. However, little information is known about the recognition of nuclear localization sequences (NLS) of these proteins. This work concerns specifically the structural studies of complexes with Imp± and NLSs peptides from proteins related to DNA repair using crystallographic and other biophysical and biochemical techniques (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

BARROS, Andréa Coelho de. Estudos estruturais com a importina-σ de mamíferos e peptídeos de sequências de localização nuclear (NLS) de proteínas envolvidas no reparo de DNA. 2015. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu Botucatu.