Human replication protein A: Global fold of the N-terminal RPA-70 domain reveals a basic cleft and flexible C-terminal linker

Doris Jacobs; Andrew Lipton; Nancy Isern; Gary Daughdrill; David Lowry; Xavier Gomes; Marc Wold

doi:10.1023/A:1008373009786

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Human replication protein A: Global fold of the N-terminal RPA-70 domain reveals a basic cleft and flexible C-terminal linker

Journal article

Peer reviewed

Human replication protein A: Global fold of the N-terminal RPA-70 domain reveals a basic cleft and flexible C-terminal linker

Doris Jacobs, Andrew Lipton, Nancy Isern, Gary Daughdrill, David Lowry, Xavier Gomes and Marc Wold

Journal of biomolecular NMR, Vol.14(4), pp.321-331

08/1999

DOI: 10.1023/A:1008373009786

PMID: 10526407

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Abstract

Human Replication Protein A (hsRPA) is required for multiple cellular processes in DNA metabolism including DNA repair, replication and recombination. It binds single-stranded DNA with high affinity and interacts specifically with multiple proteins. hsRPA forms a heterotrimeric complex composed of 70-, 32- and 14-kDa subunits (henceforth RPA70, RPA32, and RPA14). The N-terminal 168 residues of RPA70 form a structurally distinct domain that stimulates DNA polymerase α activity, interacts with several transcriptional activators including tumor suppressor p53, and during the cell cycle it signals escape from the DNA damage induced G2/M checkpoint. We have solved the global fold of the fragment corresponding to this domain (RPA70Δ169) and we find residues 8–108 of the N-terminal domain are structured. The remaining C-terminal residues are unstructured and may form a flexible linker to the DNA-binding domain of RPA70. The globular region forms a five-stranded anti-parallel β-barrel. The ends of the barrel are capped by short helices. Two loops on one side of the barrel form a large basic cleft which is a likely site for binding the acidic motifs of transcriptional activators. Many lethal or conditional lethal yeast point mutants map to this cleft, whereas no mutations with severe phenotype have been found in the linker region.

Polymer Sciences

secondary structure

Chemistry

DNA replication

RPA

RPA70

DNA recombination

Animal Anatomy / Morphology / Histology

DNA repair

backbone assignments

Details

Title: Subtitle: Human replication protein A: Global fold of the N-terminal RPA-70 domain reveals a basic cleft and flexible C-terminal linker
Creators: Doris Jacobs - Environmental Molecular Sciences Laboratory Pacific Northwest National Laboratory 902 Battelle Boulevard Richland WA 99352 U.S.A
Andrew Lipton - Environmental Molecular Sciences Laboratory Pacific Northwest National Laboratory 902 Battelle Boulevard Richland WA 99352 U.S.A
Nancy Isern - Environmental Molecular Sciences Laboratory Pacific Northwest National Laboratory 902 Battelle Boulevard Richland WA 99352 U.S.A
Gary Daughdrill - Environmental Molecular Sciences Laboratory Pacific Northwest National Laboratory 902 Battelle Boulevard Richland WA 99352 U.S.A
David Lowry - Environmental Molecular Sciences Laboratory Pacific Northwest National Laboratory 902 Battelle Boulevard Richland WA 99352 U.S.A
Xavier Gomes - Department of Biochemistry University of Iowa College of Medicine Iowa City IA 52240 U.S.A
Marc Wold - Department of Biochemistry University of Iowa College of Medicine Iowa City IA 52240 U.S.A
Resource Type: Journal article
Publication Details: Journal of biomolecular NMR, Vol.14(4), pp.321-331
Publisher: Kluwer Academic Publishers; Dordrecht
DOI: 10.1023/A:1008373009786
PMID: 10526407
ISSN: 0925-2738
eISSN: 1573-5001
Language: English
Date published: 08/1999
Academic Unit: Radiation Oncology; Biochemistry and Molecular Biology
Record Identifier: 9984024560902771

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