Differential regulation of the anti-crossover and replication fork regression activities of Mph1 by Mte1

Xue, Xu; Papusha, Alma; Choi, Kyungoh; Bonner, Jaclyn N.; Kumar, Sandeep; Niu, Hengyao; Kaur, Hardeep; Zheng, X.F. Steven; Donnianni, Roberto A.; Lichten, Michael; Zhao, Xiaolan; Ira, Grzegorz; Sung, Patrick

doi:10.1101/gad.276139.115

Cited by 17 publications

(17 citation statements)

References 52 publications

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“…Mte1 also binds directly to DNA with a preference for branched molecules, such as D loops and fork structures. We note that similar conclusions were reached in an independent study by Xue et al (2016). Deletion of MTE1 reduces CO recombination and suppresses the MMS sensitivity of mph1Δ mutant cells, suggesting that Mte1 acts upstream of Mph1 to promote a DNA repair pathway that requires Mph1.…”

Section: Discussionsupporting

confidence: 88%

Mte1 interacts with Mph1 and promotes crossover recombination and telomere maintenance

et al. 2016

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Mph1 is a member of the conserved FANCM family of DNA motor proteins that play key roles in genome maintenance processes underlying Fanconi anemia, a cancer predisposition syndrome in humans. Here, we identify Mte1 as a novel interactor of the Mph1 helicase in Saccharomyces cerevisiae. In vitro, Mte1 (Mph1-associated telomere maintenance protein 1) binds directly to DNA with a preference for branched molecules such as D loops and fork structures. In addition, Mte1 stimulates the helicase and fork regression activities of Mph1 while inhibiting the ability of Mph1 to dissociate recombination intermediates. Deletion of MTE1 reduces crossover recombination and suppresses the sensitivity of mph1Δ mutant cells to replication stress. Mph1 and Mte1 interdependently colocalize at DNA damage-induced foci and dysfunctional telomeres, and MTE1 deletion results in elongated telomeres. Taken together, our data indicate that Mte1 plays a role in regulation of crossover recombination, response to replication stress, and telomere maintenance.

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Section: Discussionsupporting

confidence: 88%

Mte1 interacts with Mph1 and promotes crossover recombination and telomere maintenance

et al. 2016

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“…Mph1 is a multifunctional protein with roles in homologous recombination ( 43 ), telomere maintenance ( 44 ), Okazaki fragment maturation ( 45 ), as well as error-free lesion bypass ( 42 , 46 ). To determine whether inability of Mph1 to mediate its functions during homologous recombination contributes to the observed elevation in A3B-induced Can R frequency in mph1 Δ strains, we deleted the Mph1-associated factor Mte1, which supports Mph1 activities during the homology-directed repair of DNA double strand breaks ( 47 – 49 ). No detectable difference was observed between the Can R frequency of mte1 Δ strains compared to wild-type yeast ( P = 0.0931).…”

Section: Resultsmentioning

confidence: 99%

Avoidance of APOBEC3B-induced mutation by error-free lesion bypass

Hoopes

Hughes

Hobson

et al. 2017

Nucleic Acids Research

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APOBEC cytidine deaminases mutate cancer genomes by converting cytidines into uridines within ssDNA during replication. Although uracil DNA glycosylases limit APOBEC-induced mutation, it is unknown if subsequent base excision repair (BER) steps function on replication-associated ssDNA. Hence, we measured APOBEC3B-induced CAN1 mutation frequencies in yeast deficient in BER endonucleases or DNA damage tolerance proteins. Strains lacking Apn1, Apn2, Ntg1, Ntg2 or Rev3 displayed wild-type frequencies of APOBEC3B-induced canavanine resistance (CanR). However, strains without error-free lesion bypass proteins Ubc13, Mms2 and Mph1 displayed respective 4.9-, 2.8- and 7.8-fold higher frequency of APOBEC3B-induced CanR. These results indicate that mutations resulting from APOBEC activity are avoided by deoxyuridine conversion to abasic sites ahead of nascent lagging strand DNA synthesis and subsequent bypass by error-free template switching. We found this mechanism also functions during telomere re-synthesis, but with a diminished requirement for Ubc13. Interestingly, reduction of G to C substitutions in Ubc13-deficient strains uncovered a previously unknown role of Ubc13 in controlling the activity of the translesion synthesis polymerase, Rev1. Our results highlight a novel mechanism for error-free bypass of deoxyuridines generated within ssDNA and suggest that the APOBEC mutation signature observed in cancer genomes may under-represent the genomic damage these enzymes induce.

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“…In addition to the role of the Smc5/6 complex in controlling Mph1 activity, Mte1 can also regulate the function of the helicase. It has been demonstrated that Mte1 binds directly to D-loops [64,65] through previously bound Mph1 to collaborate in the disappearance of Rad52 foci during DSB repair [66].…”

Section: The Mph1 Helicase Contributes To D-loop Dismantlingmentioning

confidence: 99%

Resolvases, Dissolvases, and Helicases in Homologous Recombination: Clearing the Road for Chromosome Segregation

San-Segundo

Clemente‐Blanco

2020

Genes

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The execution of recombinational pathways during the repair of certain DNA lesions or in the meiotic program is associated to the formation of joint molecules that physically hold chromosomes together. These structures must be disengaged prior to the onset of chromosome segregation. Failure in the resolution of these linkages can lead to chromosome breakage and nondisjunction events that can alter the normal distribution of the genomic material to the progeny. To avoid this situation, cells have developed an arsenal of molecular complexes involving helicases, resolvases, and dissolvases that recognize and eliminate chromosome links. The correct orchestration of these enzymes promotes the timely removal of chromosomal connections ensuring the efficient segregation of the genome during cell division. In this review, we focus on the role of different DNA processing enzymes that collaborate in removing the linkages generated during the activation of the homologous recombination machinery as a consequence of the appearance of DNA breaks during the mitotic and meiotic programs. We will also discuss about the temporal regulation of these factors along the cell cycle, the consequences of their loss of function, and their specific role in the removal of chromosomal links to ensure the accurate segregation of the genomic material during cell division.

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Differential regulation of the anti-crossover and replication fork regression activities of Mph1 by Mte1

Cited by 17 publications

References 52 publications

Mte1 interacts with Mph1 and promotes crossover recombination and telomere maintenance

Mte1 interacts with Mph1 and promotes crossover recombination and telomere maintenance

Avoidance of APOBEC3B-induced mutation by error-free lesion bypass

Resolvases, Dissolvases, and Helicases in Homologous Recombination: Clearing the Road for Chromosome Segregation

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