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Inhibition of nucleotide excision repair by anti-XPA monoclonal antibodies which interfere with binding to RPA, ERCC1, and TFIIH.

Abstract：

:The xeroderma pigmentosum group A protein (XPA) binds to three nucleotide excision repair (NER) factors: RPA, ERCC1, and TFIIH. XPA also binds preferentially to UV- or chemical carcinogen-damaged DNA. In this study, we prepared anti-XPA monoclonal antibodies and examined their effects on NER. Two clones inhibited cell-free NER reactions. The mode of inhibition appeared to differ; one clone inhibited both 5' and 3' incisions equally while the other inhibited the 5' incision more. The two clones inhibited the binding of XPA to RPA, ERCC1, and TFIIH. They did not inhibit the binding to damaged DNA either. These results suggest that the interaction of XPA with these NER factors is essential to the NER pathway. The epitopes of these antibodies were located outside of the binding regions for these NER factors. Steric hindrance or conformational changes of XPA brought about by the binding of anti-XPA IgG possibly cause the inhibitory effects.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Saijo M,Matsuda T,Kuraoka I,Tanaka K

doi

10.1016/j.bbrc.2004.07.030

subject

Has Abstract

pub_date

2004-09-03 00:00:00

pages

815-22

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(04)01522-0

journal_volume

321

pub_type

杂志文章

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