An interaction between the DNA repair factor XPA and replication protein A appears essential for nucleotide excision repair.

Abstract:

:Replication protein A (RPA) is required for simian virus 40-directed DNA replication in vitro and for nucleotide excision repair (NER). Here we report that RPA and the human repair protein XPA specifically interact both in vitro and in vivo. Mapping of the RPA-interactive domains in XPA revealed that both of the largest subunits of RPA, RPA-70 and RPA-34, interact with XPA at distinct sites. A domain involved in mediating the interaction with RPA-70 was located between XPA residues 153 and 176. Deletion of highly conserved motifs within this region identified two mutants that were deficient in binding RPA in vitro and highly defective in NER both in vitro and in vivo. A second domain mediating the interaction with RPA-34 was identified within the first 58 residues in XPA. Deletion of this region, however, only moderately affects the complementing activity of XPA in vivo. Finally, the XPA-RPA complex is shown to have a greater affinity for damaged DNA than XPA alone. Taken together, these results indicate that the interaction between XPA and RPA is required for NER but that only the interaction with RPA-70 is essential.

journal_name

Mol Cell Biol

authors

Li L,Lu X,Peterson CA,Legerski RJ

doi

10.1128/mcb.15.10.5396

subject

Has Abstract

pub_date

1995-10-01 00:00:00

pages

5396-402

issue

10

eissn

0270-7306

issn

1098-5549

journal_volume

15

pub_type

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