Recognition of helical kinks by xeroderma pigmentosum group A protein triggers DNA excision repair.

Abstract:

:The function of human XPA protein, a key subunit of the nucleotide excision repair pathway, has been examined with site-directed substitutions in its putative DNA-binding cleft. After screening for repair activity in a host-cell reactivation assay, we analyzed mutants by comparing their affinities for different substrate architectures, including DNA junctions that provide a surrogate for distorted reaction intermediates, and by testing their ability to recruit the downstream endonuclease partner. Normal repair proficiency was retained when XPA mutations abolished only the simple interaction with linear DNA molecules. By contrast, results from a K141E K179E double mutant revealed that excision is crucially dependent on the assembly of XPA protein with a sharp bending angle in the DNA substrate. These findings show how an increased deformability of damaged sites, leading to helical kinks recognized by XPA, contributes to target selectivity in DNA repair.

journal_name

Nat Struct Mol Biol

authors

Camenisch U,Dip R,Schumacher SB,Schuler B,Naegeli H

doi

10.1038/nsmb1061

keywords:

subject

Has Abstract

pub_date

2006-03-01 00:00:00

pages

278-84

issue

3

eissn

1545-9993

issn

1545-9985

pii

nsmb1061

journal_volume

13

pub_type

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