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Tytuł pozycji:

Extrinsic proofreading.

Tytuł:
Extrinsic proofreading.
Autorzy:
Zhou ZX; Genome Integrity Structural Biology Laboratory, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA.
Kunkel TA; Genome Integrity Structural Biology Laboratory, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA. Electronic address: .
Źródło:
DNA repair [DNA Repair (Amst)] 2022 Sep; Vol. 117, pp. 103369. Date of Electronic Publication: 2022 Jul 04.
Typ publikacji:
Journal Article; Review; Research Support, N.I.H., Intramural
Język:
English
Imprint Name(s):
Original Publication: Amsterdam ; New York : Elsevier, c2002-
MeSH Terms:
DNA Polymerase III*/metabolism
DNA Replication*
DNA ; DNA Polymerase II/metabolism ; Exonucleases/metabolism
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Grant Information:
Z01 ES065070 United States ImNIH Intramural NIH HHS
Contributed Indexing:
Keywords: Base substitutions; DNA polymerase; Genome stability; Mismatches; Proofreading; Replication fidelity
Substance Nomenclature:
9007-49-2 (DNA)
EC 2.7.7.7 (DNA Polymerase II)
EC 2.7.7.7 (DNA Polymerase III)
EC 3.1.- (Exonucleases)
Entry Date(s):
Date Created: 20220719 Date Completed: 20220809 Latest Revision: 20230902
Update Code:
20240104
PubMed Central ID:
PMC9561950
DOI:
10.1016/j.dnarep.2022.103369
PMID:
35850061
Czasopismo naukowe
The high fidelity of replication of the nuclear DNA genome in eukaryotes involves three processes. Correct rather than incorrect dNTPs are almost always incorporated by the three major replicases, DNA polymerases α, δ and ε. When an incorrect base is occasionally inserted, the latter Pols δ and ε also have a 3 ´ to 5 ´ exonuclease activity that can remove the mismatch to allow correct DNA synthesis to proceed. Lastly, rare mismatches that escape proofreading activity and are present in newly replicated DNA can be removed by DNA mismatch repair. In this review, we consider evidence supporting the hypothesis that the second mechanism, proofreading, can operate in two different ways. Primer terminal mismatches made by either Pol δ or Pol ε can be 'intrinsically' proofread. This mechanism occurs by direct transfer of a misinserted base made at the polymerase active site to the exonuclease active site that is located a short distance away. Intrinsic proofreading allows mismatch excision without intervening enzyme dissociation. Alternatively, considerable evidence suggests that mismatches made by any of the three replicases can also be proofread by 'extrinsic' proofreading by Pol δ. Extrinsic proofreading occurs when a mismatch made by any of the three replicases is initially abandoned, thereby allowing the exonuclease active site of Pol δ to bind directly to and remove the mismatch before replication continues. Here we review the evidence that extrinsic proofreading significantly enhances the fidelity of nuclear DNA replication, and we then briefly consider the implications of this process for evolution and disease.
(Published by Elsevier B.V.)

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