title: Identification of the DNA-Binding Domains of Human Replication Protein A That Recognize G-Quadruplex DNA.
abstract: Replication protein A (RPA), a key player in DNA metabolism, has 6 single-stranded DNA-(ssDNA-) binding domains (DBDs) A-F. SELEX experiments with the DBDs-C, -D, and -E retrieve a 20-nt G-quadruplex forming sequence. Binding studies show that RPA-DE binds preferentially to the G-quadruplex DNA, a unique preference not observed with other RPA constructs. Circular dichroism experiments show that RPA-CDE-core can unfold the G-quadruplex while RPA-DE stabilizes it. Binding studies show that RPA-C binds pyrimidine- and purine-rich sequences similarly. This difference between RPA-C and RPA-DE binding was also indicated by the inability of RPA-CDE-core to unfold an oligonucleotide containing a TC-region 5' to the G-quadruplex. Molecular modeling studies of RPA-DE and telomere-binding proteins Pot1 and Stn1 reveal structural similarities between the proteins and illuminate potential DNA-binding sites for RPA-DE and Stn1. These data indicate that DBDs of RPA have different ssDNA recognition properties.
authors.affiliation: The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 987696 Nebraska Medical Center, Omaha, NE 68198-7696, USA.
authors.forename: Aishwarya
authors.initials: A
authors.lastname: Prakash
authors.forename: Amarnath
authors.initials: A
authors.lastname: Natarajan
authors.forename: Luis A
authors.initials: LA
authors.lastname: Marky
authors.forename: Michel M
authors.initials: MM
authors.lastname: Ouellette
authors.forename: Gloria E O
authors.initials: GE
authors.lastname: Borgstahl