Age dependent decline in the 3'-->5' exonuclease activity involved in proofreading during DNA synthesis.

Abstract:

:A 3'-->5' exonuclease found in rat liver excises mispaired nucleotides at the 3'-hydroxyl end of primer chains such as poly dA-d(T9-C). Consequently, the priming activity of the chain from which the mispaired base was cut is greatly increased during DNA synthesis. These results suggest that the 3'-->5' exonuclease acts as a proofreading enzyme during DNA synthesis. The activity of this 3'-->5' exonuclease in the liver of 24-month-old rats is approximately 30% lower than the activity found in 4-month-old rats. Furthermore, non-complementary nucleotide incorporations by DNA polymerases from aged rats are observed during DNA synthesis on poly dA-dT10. The number of misincorporations decreases in the presence of the 3'-->5' exonuclease, but not all errors are prevented even when DNA polymerase and 3'-->5' exonuclease are added at an activity ratio similar to that found in vivo. The data suggest that declines in both the fidelity of DNA polymerase and the 3'-->5' exonuclease activity related to proofreading during the aging process lead to a higher frequency of base misincorporations during DNA replication.

journal_name

Mech Ageing Dev

authors

Taguchi T,Fukuda M,Toda T,Ohashi M

doi

10.1016/s0047-6374(98)00083-9

subject

Has Abstract

pub_date

1998-09-15 00:00:00

pages

75-87

issue

1-2

eissn

0047-6374

issn

1872-6216

pii

S0047-6374(98)00083-9

journal_volume

105

pub_type

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