DNA Ligases:  Structure, Reaction Mechanism, and Function

Tomkinson, Alan E.; Vijayakumar, Sangeetha; Pascal, John M.; Ellenberger, Tom

doi:10.1021/cr040498d

Cited by 251 publications

(244 citation statements)

References 131 publications

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“…These enzymes are defined by the essential lysine residue situated within motif I, the first of a series of conserved colinear motifs (Doherty and Suh 2000;Shuman and Lima 2004;Tomkinson et al 2006). Closer examination of the sequences within the motifs of FaLig confirmed that it contains all amino acids that are essential for the function of nucleotidyl transferases and all amino acids that are highly conserved in predicted bacterial ATP-dependent DNA ligases (Wilkinson et al 2001) (Fig.…”

Section: Identification Of An Atp-dependent Dna Ligase Within the Genmentioning

confidence: 94%

“…Recent studies identify that DNA ligases may join breaks in a variety of double-stranded nucleic acids (Martins and Shuman 2004;Pascal et al 2004;Sekiguchi and Shuman 1997;Sriskanda and Shuman 1998;Tomkinson et al 2006), with the range of active substrates varying compared to enzymes characterized as ''RNA'' ligases (Bullard and Bowater 2006). To assess how FaLig fitted into these categories, we analysed its nick-joining activity on a range of substrates.…”

Section: Biochemical Characterization Of Nick-joining By Faligmentioning

confidence: 99%

“…7b). The same range of substrates was ligated by features Tomkinson et al 2006;Wilkinson et al 2001). Recently, however, characterization of DNA ligases from some archaea have identified unexpected features, particularly in relation to the role of the co-factor in enzyme function (Jeon and Ishikawa 2003;Nakatani et al 2000;Rolland et al 2004;Zhao et al 2006).…”

Section: Biochemical Characterization Of Nick-joining By Faligmentioning

confidence: 99%

“…For the Archaea, the AMP moiety is generally provided by ATP (EC 6.5.1.1), while the essential DNA ligases of bacteria obtain this from NAD + (EC 6.5.1.2) (Wilkinson et al 2001). High resolution structures of several DNA ligases confirm that they exhibit a modular structure, with the common core required for adenylation linked to other domains that bind substrate (Doherty and Suh 2000;Shuman and Lima 2004;Tomkinson et al 2006).…”

Section: Introductionmentioning

confidence: 99%

“…These enzymes act to join breaks in the backbone of DNA and are essential for all cellular organisms due to the requirement for completion of replication, but they also participate in the repair and recombination of DNA (Doherty and Suh 2000;Shuman and Lima 2004;Tomkinson et al 2006;Wilkinson et al 2001). All nucleotidyl transferases are believed to operate through similar biochemical mechanisms consisting of three separate steps (Doherty and Suh 2000;Lehman 1974;Shuman and Lima 2004;Timson et al 2000;Wilkinson et al 2001).…”

Section: Introductionmentioning

confidence: 99%

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Characterization of an ATP-dependent DNA ligase from the acidophilic archaeon “Ferroplasma acidarmanus” Fer1

et al. 2006

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Section: Identification Of An Atp-dependent Dna Ligase Within the Genmentioning

confidence: 94%

Section: Biochemical Characterization Of Nick-joining By Faligmentioning

confidence: 99%

Section: Biochemical Characterization Of Nick-joining By Faligmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Characterization of an ATP-dependent DNA ligase from the acidophilic archaeon “Ferroplasma acidarmanus” Fer1

et al. 2006

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Proliferating cell nuclear antigen restores the enzymatic activity of a DNA ligase I deficient in DNA binding

Trasviña-Arenas¹,

Cardona-Félix²,

Azuara-Licéaga

et al. 2017

FEBS Open Bio

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Proliferating cell nuclear antigen (PCNA) coordinates multienzymatic reactions by interacting with a variety of protein partners. Family I DNA ligases are multidomain proteins involved in sealing of DNA nicks during Okazaki fragment maturation and DNA repair. The interaction of DNA ligases with the interdomain connector loop (IDCL) of PCNA through its PCNA‐interacting peptide (PIP box) is well studied but the role of the interacting surface between both proteins is not well characterized. In this work, we used a minimal DNA ligase I and two N‐terminal deletions to establish that DNA binding and nick‐sealing stimulation of DNA ligase I by PCNA are not solely dependent on the PIP box–IDCL interaction. We found that a truncated DNA ligase I with a deleted PIP box is stimulated by PCNA. Furthermore, the activity of a DNA ligase defective in DNA binding is rescued upon PCNA addition. As the rate constants for single‐turnover ligation for the full‐length and truncated DNA ligases are not affected by PCNA, our data suggest that PCNA stimulation is achieved by increasing the affinity for nicked DNA substrate and not by increasing catalytic efficiency. Surprisingly C‐terminal mutants of PCNA are not able to stimulate nick‐sealing activity of Entamoeba histolytica DNA ligase I. Our data support the notion that the C‐terminal region of PCNA may be involved in promoting an allosteric transition in E. histolytica DNA ligase I from a spread‐shaped to a ring‐shaped structure. This study suggests that the ring‐shaped PCNA is a binding platform able to stabilize coevolved protein–protein interactions, in this case an interaction with DNA ligase I.

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