A Mutation in EXO1 Defines Separable Roles in DNA Mismatch Repair and Post-replication Repair

Overview

Journal DNA Repair (Amst)

Publisher Elsevier

Specialties Biochemistry
Molecular Biology

Date 2007 Jul 3

PMID 17602897

Citations 33

Authors

Phuoc T Tran

Julien P Fey

Naz Erdeniz

Lionel Gellon

Serge Boiteux

R Michael Liskay

Affiliations

Soon will be listed here.

Abstract

Replication forks stall at DNA lesions or as a result of an unfavorable replicative environment. These fork stalling events have been associated with recombination and gross chromosomal rearrangements. Recombination and fork bypass pathways are the mechanisms accountable for restart of stalled forks. An important lesion bypass mechanism is the highly conserved post-replication repair (PRR) pathway that is composed of error-prone translesion and error-free bypass branches. EXO1 codes for a Rad2p family member nuclease that has been implicated in a multitude of eukaryotic DNA metabolic pathways that include DNA repair, recombination, replication, and telomere integrity. In this report, we show EXO1 functions in the MMS2 error-free branch of the PRR pathway independent of the role of EXO1 in DNA mismatch repair (MMR). Consistent with the idea that EXO1 functions independently in two separate pathways, we defined a domain of Exo1p required for PRR distinct from those required for interaction with MMR proteins. We then generated a point mutant exo1 allele that was defective for the function of Exo1p in MMR due to disrupted interaction with Mlh1p, but still functional for PRR. Lastly, by using a compound exo1 mutant that was defective for interaction with Mlh1p and deficient for nuclease activity, we provide further evidence that Exo1p plays both structural and catalytic roles during MMR.

Citing Articles

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Action-At-A-Distance in DNA Mismatch Repair: Mechanistic Insights and Models for How DNA and Repair Proteins Facilitate Long-Range Communication.

Collingwood B, Witte S, Manhart C Biomolecules. 2024; 14(11).

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Exo1 cooperates with Tel1/ATM in promoting recombination events at DNA replication forks.

Galli M, Frigerio C, Colombo C, Casari E, Longhese M, Clerici M iScience. 2024; 27(8):110410.

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EXO1 and DNA2-mediated ssDNA gap expansion is essential for ATR activation and to maintain viability in BRCA1-deficient cells.

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The Dmc1 recombinase physically interacts with and promotes the meiotic crossover functions of the Mlh1-Mlh3 endonuclease.

Pannafino G, Chen J, Mithani V, Payero L, Gioia M, Crickard J Genetics. 2024; 227(3).

PMID: 38657110 PMC: 11228845. DOI: 10.1093/genetics/iyae066.

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