8-Chloro-dGTP, a hypochlorous acid-modified nucleotide, is hydrolyzed by hMTH1, the human MutT homolog.

Abstract:

:The human mutT homolog, hMTH1, suppresses spontaneous mutations by degrading the endogeneous mutagen, 8-hydroxy-dGTP. We previously reported the broad substrate specificity of hMTH1, which also degrades the oxidatively damaged purine nucleotides, 2-hydroxy-dATP, 8-hydroxy-dATP, 2-hydroxy-ATP, and 8-hydroxy-GTP, in addition to 8-hydroxy-dGTP. In this paper, we describe the hMTH1 activity for 8-chloro-dGTP, which could be formed in inflamed tissue by the reaction of dGTP with hypochlorous acid, a product of myeloperoxidase from activated human neutrophils. The hMTH1 protein was mixed with 1-20 microM of 8-chloro-dGTP and 8-hydroxy-dGTP, and the reaction products were quantified by anion-exchange HPLC to measure the pyrophosphatase reaction rate. The kinetic parameters revealed that 8-chloro-dGTP was degraded by hMTH1 with 50% efficiency as compared with that of 8-hydroxy-dGTP. This result suggests that 8-chloro-dGTP is an intrinsic substrate for hMTH1.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Fujikawa K,Yakushiji H,Nakabeppu Y,Suzuki T,Masuda M,Ohshima H,Kasai H

doi

10.1016/s0014-5793(02)02240-8

keywords:

subject

Has Abstract

pub_date

2002-02-13 00:00:00

pages

149-51

issue

1-3

eissn

0014-5793

issn

1873-3468

pii

S0014579302022408

journal_volume

512

pub_type

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