Complex of repair DNA polymerase β with autonomous 3′→5′ exonuclease shows increased accuracy of DNA synthesis

Belyakova, N. V.; Kravetskaya, T. P.; Legina, O. K.; Ronzhina, N. L.; Shevelev, I. A.; Krutyakov, V. M.

doi:10.1134/s1062359007050019

Cited by 1 publication

(1 citation statement)

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“…Intriguingly, NM23-H1 is an autonomous 3′–5′ EXO [5,6,8], an enzymatic function often implicated in enhancing the proofreading capacities of error-prone DNA polymerases during translesion repair (TLS). Thus, it is possible NM23 may have a direct proofreading function during TLS or as a facilitory role in protein complexes associated with DNA during TLS [8,36,37]. Mutation spectral analysis of the CAN1 gene revealed increased frameshift mutations in ynk1 Δ after UV treatment.…”

Section: Discussionmentioning

confidence: 99%

YNK1, the yeast homolog of human metastasis suppressor NM23, is required for repair of UV radiation- and etoposide-induced DNA damage

Jarrett

Craven

Kaetzel

2009

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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In humans, NM23-H1 is a metastasis suppressor whose expression is reduced in metastatic melanoma and breast carcinoma cells, and which possesses the ability to inhibit metastatic growth without significant impact on the transformed phenotype. NM23-H1 exhibits three enzymatic activities in vitro, each with potential to maintain genomic stability, a 3′-5′exonuclease and two kinases, nucleoside diphosphate kinase (NDPK), and protein histidine kinase. Herein we have investigated the potential contributions of NM23 proteins to DNA repair in the yeast, Saccharomyces cerevisiae, which contains a single NM23 homolog, YNK1. Ablation of YNK1 delayed repair of UVand etoposide-induced nuclear DNA damage by 3-6 hrs. However, YNK1 had no impact upon the kinetics of MMS-induced DNA repair. Furthermore, YNK1 was not required for repair of mitochondrial DNA damage. To determine whether the nuclear DNA repair deficit manifested as an increase in mutation frequency, the CAN1 forward assay was employed. An YNK1 deletion was associated with increased mutation rates following treatment with either UV (2.6x) or MMS (1.6x). Mutation spectral analysis further revealed significantly increased rates of base substitution and frameshift mutations following UV treatment in the ynk1Δ strain. This study indicates a novel role for YNK1 in DNA repair in yeast, and suggests an anti-mutator function that may contribute to the metastasis suppressor function of NM23-H1 in humans.

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