scholarly journals Deaminated purine bypass by DNA polymerase η

2021 ◽  
Vol 478 (7) ◽  
pp. 1309-1313
Author(s):  
Antonina Andreeva

A recent work by Jung and colleagues (Biochem J.477, 4797–4810) provides an explanation of how DNA polymerase η replicates through deaminated purine bases such as xanthine and hypoxanthine. This commentary discusses the crystal structures of the polymerase η complexes that implicate the role of tautomerism in the bypass of these DNA lesions.

2015 ◽  
Vol 29 (24) ◽  
pp. 2588-2602 ◽  
Author(s):  
Jung-Hoon Yoon ◽  
Jeseong Park ◽  
Juan Conde ◽  
Maki Wakamiya ◽  
Louise Prakash ◽  
...  

Translesion synthesis (TLS) DNA polymerases (Pols) promote replication through DNA lesions; however, little is known about the protein factors that affect their function in human cells. In yeast, Rev1 plays a noncatalytic role as an indispensable component of Polζ, and Polζ together with Rev1 mediates a highly mutagenic mode of TLS. However, how Rev1 functions in TLS and mutagenesis in human cells has remained unclear. Here we determined the role of Rev1 in TLS opposite UV lesions in human and mouse fibroblasts and showed that Rev1 is indispensable for TLS mediated by Polη, Polι, and Polκ but is not required for TLS by Polζ. In contrast to its role in mutagenic TLS in yeast, Rev1 promotes predominantly error-free TLS opposite UV lesions in humans. The identification of Rev1 as an indispensable scaffolding component for Polη, Polι, and Polκ, which function in TLS in highly specialized ways opposite a diverse array of DNA lesions and act in a predominantly error-free manner, implicates a crucial role for Rev1 in the maintenance of genome stability in humans.


2001 ◽  
Vol 21 (10) ◽  
pp. 3558-3563 ◽  
Author(s):  
Robert E. Johnson ◽  
Lajos Haracska ◽  
Satya Prakash ◽  
Louise Prakash

ABSTRACT UV light-induced DNA lesions block the normal replication machinery. Eukaryotic cells possess DNA polymerase η (Polη), which has the ability to replicate past a cis-syn thymine-thymine (TT) dimer efficiently and accurately, and mutations in human Polη result in the cancer-prone syndrome, the variant form of xeroderma pigmentosum. Here, we test Polη for its ability to bypass a (6-4) TT lesion which distorts the DNA helix to a much greater extent than acis-syn TT dimer. Opposite the 3′ T of a (6-4) TT photoproduct, both yeast and human Polη preferentially insert a G residue, but they are unable to extend from the inserted nucleotide. DNA Polζ, essential for UV induced mutagenesis, efficiently extends from the G residue inserted opposite the 3′ T of the (6-4) TT lesion by Polη, and Polζ inserts the correct nucleotide A opposite the 5′ T of the lesion. Thus, the efficient bypass of the (6-4) TT photoproduct is achieved by the combined action of Polη and Polζ, wherein Polη inserts a nucleotide opposite the 3′ T of the lesion and Polζ extends from it. These biochemical observations are in concert with genetic studies in yeast indicating that mutations occur predominantly at the 3′ T of the (6-4) TT photoproduct and that these mutations frequently exhibit a 3′ T→C change that would result from the insertion of a G opposite the 3′ T of the (6-4) TT lesion.


2019 ◽  
Vol 489 (1) ◽  
pp. 93-98
Author(s):  
I. A. Vasil’eva ◽  
N. A. Moor ◽  
O. I. Lavrik

Influence of XRCC1 protein oxidation on the modification of proteins catalyzed by poly(ADP‑ribose)polyme-rases (PARP1 and PARP2) has been studied for the first time. XRCC1, PARP1 and PARP2 are responsible for coordination of multistep repair of most abundant DNA lesions, functioning as scaffold proteins. We have shown that the XRCC1 oxidation reduces the efficiency of its ADP‑ribosylation and the protein affinity for poly(ADP‑ribose). The ADP‑ribose modification of various XRCC1 forms is enhanced in the presence of DNA polymerase b (Polb) capable to form a stable complex with XRCC1. The oxidation suppresses the inhibiting activity of XRCC1 and its complex with Polb towards the automodification of PARP1 and PARP2 that may enhance the efficiency of repair. The results of this study indicate that the oxidation of XRCC1 play a role in fine regulation of poly(ADP‑ribosyl)ation levels of proteins and their coordinating functions in the DNA repair.


2021 ◽  
Vol 4 (4) ◽  
pp. e202000900
Author(s):  
Jung-Hoon Yoon ◽  
Debashree Basu ◽  
Karthi Sellamuthu ◽  
Robert E Johnson ◽  
Satya Prakash ◽  
...  

By extending synthesis opposite from a diverse array of DNA lesions, DNA polymerase (Pol) ζ performs a crucial role in translesion synthesis (TLS). In yeast and cancer cells, Rev1 functions as an indispensable scaffolding component of Polζ and it imposes highly error-prone TLS upon Polζ. However, for TLS that occurs during replication in normal human cells, Rev1 functions instead as a scaffolding component of Pols η, ι, and κ and Rev1-dependent TLS by these Pols operates in a predominantly error-free manner. The lack of Rev1 requirement for Polζ function in TLS in normal cells suggested that some other protein substitutes for this Rev1 role. Here, we identify a novel role of Polλ as an indispensable scaffolding component of Polζ. TLS studies opposite a number of DNA lesions support the conclusion that as an integral component, Polλ adapts Polζ-dependent TLS to operate in a predominantly error-free manner in human cells, essential for genome integrity and cellular homeostasis.


2018 ◽  
Vol 68 (2) ◽  
pp. 498-516
Author(s):  
Neil O'Sullivan

Of the hundreds of Greek common nouns and adjectives preserved in our MSS of Cicero, about three dozen are found written in the Latin alphabet as well as in the Greek. So we find, alongside συμπάθεια, also sympathia, and ἱστορικός as well as historicus. This sort of variation has been termed alphabet-switching; it has received little attention in connection with Cicero, even though it is relevant to subjects of current interest such as his bilingualism and the role of code-switching and loanwords in his works. Rather than addressing these issues directly, this discussion sets out information about the way in which the words are written in our surviving MSS of Cicero and takes further some recent work on the presentation of Greek words in Latin texts. It argues that, for the most part, coherent patterns and explanations can be found in the alphabetic choices exhibited by them, or at least by the earliest of them when there is conflict in the paradosis, and that this coherence is evidence for a generally reliable transmission of Cicero's original choices. While a lack of coherence might indicate unreliable transmission, or even an indifference on Cicero's part, a consistent pattern can only really be explained as an accurate record of coherent alphabet choice made by Cicero when writing Greek words.


Author(s):  
Daniel Leech-Wilkinson

The concept of shape is widely used by musicians in talking and thinking about performance, yet the mechanisms that afford links between music and shape are little understood. Work on the psychodynamics of everyday life by Daniel Stern and on embodiment by Mark Johnson suggests relationships between the multiple dynamics of musical sound and the dynamics of feeling and motion. Recent work on multisensory and precognitive sensory perception and on the role of bimodal neurons in the sensorimotor system helps to explain how shape, as a percept representing changing quantity in any sensory mode, may be invoked by dynamic processes at many stages of perception and cognition. These processes enable ‘shape’ to do flexible and useful work for musicians needing to describe the quality of musical phenomena that are fundamental to everyday musical practice and yet too complex to calculate during performance.


Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1083
Author(s):  
Adhirath Sikand ◽  
Malgorzata Jaszczur ◽  
Linda B. Bloom ◽  
Roger Woodgate ◽  
Michael M. Cox ◽  
...  

In the mid 1970s, Miroslav Radman and Evelyn Witkin proposed that Escherichia coli must encode a specialized error-prone DNA polymerase (pol) to account for the 100-fold increase in mutations accompanying induction of the SOS regulon. By the late 1980s, genetic studies showed that SOS mutagenesis required the presence of two “UV mutagenesis” genes, umuC and umuD, along with recA. Guided by the genetics, decades of biochemical studies have defined the predicted error-prone DNA polymerase as an activated complex of these three gene products, assembled as a mutasome, pol V Mut = UmuD’2C-RecA-ATP. Here, we explore the role of the β-sliding processivity clamp on the efficiency of pol V Mut-catalyzed DNA synthesis on undamaged DNA and during translesion DNA synthesis (TLS). Primer elongation efficiencies and TLS were strongly enhanced in the presence of β. The results suggest that β may have two stabilizing roles: its canonical role in tethering the pol at a primer-3’-terminus, and a possible second role in inhibiting pol V Mut’s ATPase to reduce the rate of mutasome-DNA dissociation. The identification of umuC, umuD, and recA homologs in numerous strains of pathogenic bacteria and plasmids will ensure the long and productive continuation of the genetic and biochemical journey initiated by Radman and Witkin.


2021 ◽  
pp. 089331892199807
Author(s):  
Jonathan Clifton ◽  
Fernando Fachin ◽  
François Cooren

To date there has been little work that uses fine-grained interactional analyses of the in situ doing of leadership to make visible the role of non-human as well as human actants in this process. Using transcripts of naturally-occurring interaction as data, this study seeks to show how leadership is co-achieved by artefacts as an in-situ accomplishment. To do this we situate this study within recent work on distributed leadership and argue that it is not only distributed across human actors, but also across networks that include both human and non-human actors. Taking a discursive approach to leadership, we draw on Actor Network Theory and adopt a ventriloquial approach to sociomateriality as inspired by the Montreal School of organizational communication. Findings indicate that artefacts “do” leadership when a hybrid presence is made relevant to the interaction and when this presence provides authoritative grounds for influencing others to achieve the group’s goals.


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