Efficient Bypass of a Thymine-Thymine Dimer by Yeast DNA Polymerase, Polη

Johnson, Robert E.; Prakash, Satya; Prakash, Louise

doi:10.1126/science.283.5404.1001

Cited by 720 publications

(745 citation statements)

References 15 publications

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“…RAD30 has been implicated in an error-free form of translesion synthesis [39,40] that some have placed in the PRR pathway [41]. Neither of these genes demonstrated any sensitivity to low dose MMS as single mutants.…”

Section: Epistasis Analysis Defines a Role For Exo1 In The Mms2 Errormentioning

confidence: 99%

A mutation in EXO1 defines separable roles in DNA mismatch repair and post-replication repair

et al. 2007

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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 postreplication 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.

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Section: Epistasis Analysis Defines a Role For Exo1 In The Mms2 Errormentioning

confidence: 99%

A mutation in EXO1 defines separable roles in DNA mismatch repair and post-replication repair

et al. 2007

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“…Translesion replication, one of the strategies used to overcome this inhibition, employs specialized DNA polymerases to extend the nascent strand at blocked forks. In most cases in yeast, such extension is likely to be performed by Pol z, though DNA polymerase eta (Pol Z), encoded by RAD30 (McDonald et al 1997), is probably used with some lesions, such as a bipyrimidine cyclobutane dimer (Johnson et al 1999). While translesion replication using Pol z and Rev1p can promote viability, it nevertheless carries the penalty of reduced ¢delity, the combined result of using a less accurate enzyme on a distorted template; the process is therefore appreciably mutagenic.…”

Section: Introductionmentioning

confidence: 99%

Mutagenesis in eukaryotes dependent on DNA polymerase zeta and Rev1p

Lawrence

Maher

2001

Phil. Trans. R. Soc. Lond. B

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DNA polymerase zeta (Pol z) and Rev1p carry out translesion replication in budding yeast, Saccharomyces cerevisiae, and are jointly responsible for almost all base pair substitution and frameshift mutations induced by DNA damage in this organism. In addition, Pol z is responsible for the majority of spontaneous mutations in yeast and has been proposed as the enzyme responsible for somatic hypermutability. Pol z, a non-processive enzyme that lacks a 3' to 5' exonuclease proofreading activity, is composed of Rev3p, the catalytic subunit, and a second subunit encoded by REV7. In keeping with its role, extension by Pol z is relatively tolerant of abnormal DNA structure at the primer terminus and is much more capable of extension from terminal mismatches than yeast DNA polymerase alpha (Pol a). Rev1p is a bifunctional enzyme that possesses a deoxycytidyl transferase activity that incorporates deoxycytidyl opposite abasic sites in the template and a second, at present poorly de¢ned, activity that is required for the bypass of a variety of lesions as well as abasic sites. Human homologues of the yeast REV1 and REV3 have been identi¢ed and, based on the phenotype of cells producing antisense RNA to one or other of these genes, their products appear also to be employed in translation replication and spontaneous mutagenesis. We suggest that Pol z is best regarded as a replication enzyme, albeit one that is used only intermittently, that promotes extension at forks the progress of which is blocked for any reason, whether the presence of an unedited terminal mismatch or unrepaired DNA lesion.

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“…80 Defects in XPV lead to development of the xeroderma pigmentosum variant disorder characterized by sensitivity to UV-irradiation despite an active NER repair pathway. 79,80 The XPV polymerase is a trans-lesion polymerase that allows DNA synthesis to bypass UV photoproducts in an error-free manner [81][82][83] and has been shown to physically interact with pol ι, another bypass polymerase. 82 XPV associates with the replication machinery during DNA replication and interacts specifically with mono-ubiquitinated PCNA through two interaction sites on the polymerase.…”

Section: Cutting It Out: Xpg and Xpfmentioning

confidence: 99%

Other Proteins Interacting with XP Proteins

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Molecular Mechanisms of Xeroderma Pigmentosum

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Efficient Bypass of a Thymine-Thymine Dimer by Yeast DNA Polymerase, Polη

Cited by 720 publications

References 15 publications

A mutation in EXO1 defines separable roles in DNA mismatch repair and post-replication repair

A mutation in EXO1 defines separable roles in DNA mismatch repair and post-replication repair

Mutagenesis in eukaryotes dependent on DNA polymerase zeta and Rev1p

Other Proteins Interacting with XP Proteins

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