Temporally distinct translesion synthesis pathways for ultraviolet light-induced photoproducts in the mammalian genome

Temviriyanukul, Piya; Hees-Stuivenberg, Sandrine van; Delbos, Frédéric; Jacobs, Heinz; Wind, Niels de; Jansen, Jacob G.

doi:10.1016/j.dnarep.2012.03.007

Cited by 36 publications

(57 citation statements)

References 59 publications

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“…Possibly, defects in an early, mutagenic, translesion synthesis pathway, as observed in Rev1 BRCT -mutant mouse cells [63], may channel lesion bypass into an error-free DNA damage avoidance pathway, such as DNA template switching. Also remarkably, in mammalian cells, the BRCT region of Rev1 is much more important for tolerance of benzo(a)pyrene diolepoxide than of hydroxynonenal or UV light [64,65]. This result indicates that different lesions may require different Rev1 BRCT domain-dependent bypass pathways.…”

Section: Rev1 Pol and Genome Stabilitymentioning

confidence: 83%

“…In addition to the defect in translesion synthesis at bulky and helix-distorting nucleotide lesions, Rev1 KO or Rev3 KO cells are also defective in the replication of secondary DNA structures including G-quadruplex DNA [72,73], hairpin structures [74] or common fragile sites [75], that form a major hurdle for the processive DNA polymerases ␦ and . The exposure of Rev1 KO or Rev3 KO cells to DNA damaging agents results in the induction of chromosome fragment-containing micronuclei, DNA replicationassociated chromatid breaks and other types of chromosomal aberrations, all indicative for the accumulation of double stranded DNA breaks (DSBs) [64,65,[67][68][69]. The presence of high numbers of DSBs in Rev1 KO and Rev3 KO cells might not only reflect the defect in translesion synthesis but also a role of Rev1 and Rev3 in repair of these DSBs.…”

Section: Rev1 Pol and Genome Stabilitymentioning

confidence: 97%

“…This result indicates that different lesions may require different Rev1 BRCT domain-dependent bypass pathways. Vertebrate cells deficient for Rev1 or Pol display hypersensitivity to DNA damaging agents, including UV light, benzo(a)pyrene diolepoxide, 4-nitroquinoline-1-oxide, the cross-linking agent cisplatin, methylating agents, H 2 O 2 , hydroxynonenal, nitrogen oxide and ionizing radiation [63][64][65][66][67][68][69][70][71]. Of note, mammalian and chicken Rev3 KO cells are usually more sensitive to DNA damage than Rev1 KO cells, in agreement with the differential phenotypes of the Rev1 and Rev3 knockout mice [64,65,68].…”

Section: Rev1 Pol and Genome Stabilitymentioning

confidence: 99%

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Roles of mutagenic translesion synthesis in mammalian genome stability, health and disease

2015

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Section: Rev1 Pol and Genome Stabilitymentioning

confidence: 83%

Section: Rev1 Pol and Genome Stabilitymentioning

confidence: 97%

Section: Rev1 Pol and Genome Stabilitymentioning

confidence: 99%

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Roles of mutagenic translesion synthesis in mammalian genome stability, health and disease

2015

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“…Such behavior (referred to as "on the fly" TLS) was first observed in DT40 avian cells irradiated with UV and, indeed, found to be independent of PCNA monoubiquitination (58). Recent cellular studies suggest that ubiquitination-independent TLS events occur in murine (24,59) and human cells (60) irradiated with UV, perhaps in a similar manner. However, monoubiquitination of PCNA is required for optimal TLS in mammalian cells (24).…”

Section: Discussionmentioning

confidence: 99%

Stability of the human polymerase δ holoenzyme and its implications in lagging strand DNA synthesis

Hedglin

Pandey

Benkovic

2016

Proc. Natl. Acad. Sci. U.S.A.

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In eukaryotes, DNA polymerase δ (pol δ) is responsible for replicating the lagging strand template and anchors to the proliferating cell nuclear antigen (PCNA) sliding clamp to form a holoenzyme. The stability of this complex is integral to every aspect of lagging strand replication. Most of our understanding comes from Saccharomyces cerevisae where the extreme stability of the pol δ holoenzyme ensures that every nucleobase within an Okazaki fragment is faithfully duplicated before dissociation but also necessitates an active displacement mechanism for polymerase recycling and exchange. However, the stability of the human pol δ holoenzyme is unknown. We designed unique kinetic assays to analyze the processivity and stability of the pol δ holoenzyme. Surprisingly, the results indicate that human pol δ maintains a loose association with PCNA while replicating DNA. Such behavior has profound implications on Okazaki fragment synthesis in humans as it limits the processivity of pol δ on undamaged DNA and promotes the rapid dissociation of pol δ from PCNA on stalling at a DNA lesion.lagging strand | stability | PCNA | DNA polymerase delta | translesion DNA synthesis D uring S-phase of the cell cycle, genomic DNA must be faithfully copied in a short period. Replicative DNA polymerases (pols) alone are distributive and must anchor to ringshaped sliding clamps to achieve the high degree of processivity required for efficient DNA replication. The highly conserved toroidal structure of sliding clamps has a central cavity large enough to encircle double-stranded DNA (dsDNA) and slide freely along it. Thus, such an association effectively tethers the pol to DNA, substantially increasing the extent of continuous replication. The eukaryotic sliding clamp, proliferating cell nuclear antigen (PCNA), is trimer of identical subunits aligned head-to-tail, forming a ring with two structurally distinct faces. Each subunit consists of two independent domains connected by an interdomain connecting loop (IDCL). The "front" face of the homotrimeric PCNA ring contains all IDCLs and is a platform for interaction with the eukaryotic replicative pols, e and δ, which are responsible for the faithful replication of the leading and lagging strands, respectively (1, 2). Specifically, the well-conserved PCNA-interacting peptide (PIP) box within replicative pols makes extensive contact with an IDCL of PCNA and displays conserved residues that "plug" into the proximal hydrophobic patches. The amino acid sequence of a canonical PIP box is QXXhXXaa, where X represents any amino acid, h is a hydrophobic residue (usually L, I, or M), and a is an aromatic residue (usually F or Y) (3).Unlike the leading strand, the lagging strand is synthesized discontinuously in short Okazaki fragments that are processed and ligated together to form a continuous strand (4). In eukaryotes, each Okazaki fragment is initiated by the bifunctional DNA pol α/primase complex that lays down cRNA/DNA hybrid primers every 100-250 nucleotides (nt) on the exposed template for the l...

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“…It can efficiently bypass (6-4 TT) photoproducts Rev1 has template deoxycitidyltransferase activity and can incorporate C opposite G or any noncoding lesion like an abasic site in the DNA template [Nelson et al, 1996;Lin et al, 1999;Vaisman et al, 2004]. Rev1 is required for the bypass of (6-4 TT) photoproducts [Temviriyanukul et al, 2012]. Pol f is required for UV-induced mutagenesis and it can efficiently extend mismatched primer termini or primers blocked whose extension is blocked by noncoding or helix distorting lesions.…”

Section: Dna Damage Tolerancementioning

confidence: 99%

Mouse models of DNA polymerases

Menezes¹,

Sweasy²

2012

Environ and Mol Mutagen

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In 1956, Arthur Kornberg discovered the mechanism of the biological synthesis of DNA and was awarded the Nobel Prize in Physiology or Medicine in 1959 for this contribution, which included the isolation and characterization of Escherichia coli DNA polymerase I. Now there are 15 known DNA polymerases in mammalian cells that belong to four different families. These DNA polymerases function in many different cellular processes including DNA replication, DNA repair, and damage tolerance. Several biochemical and cell biological studies have provoked a further investigation of DNA polymerase function using mouse models in which polymerase genes have been altered using gene-targeting techniques. The phenotypes of mice harboring mutant alleles reveal the prominent role of DNA polymerases in embryogenesis, prevention of premature aging, and cancer suppression. Environ. Mol. Mutagen. 53:645-665, 2012. V V C 2012 Wiley Periodicals, Inc.

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Temporally distinct translesion synthesis pathways for ultraviolet light-induced photoproducts in the mammalian genome

Cited by 36 publications

References 59 publications

Roles of mutagenic translesion synthesis in mammalian genome stability, health and disease

Roles of mutagenic translesion synthesis in mammalian genome stability, health and disease

Stability of the human polymerase δ holoenzyme and its implications in lagging strand DNA synthesis

Mouse models of DNA polymerases

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