LIG3 (Ligase III) ligates nascent mitochondrial DNA strands

Stable Identifier
R-HSA-9914903
Type
Reaction [transition]
Species
Homo sapiens
Compartment
mitochondrial matrix
ReviewStatus
5/5
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LIG3 (Ligase III) ligates nascent mitochondrial DNA strands
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Ligase III (LIG3-1) ligates single-stranded breaks in double-stranded DNA (Cotner-Gohara et al. 2010, Kukshal et al. 2015, McNally and O'Brien 2017). After the RNA primers are removed from the 5' ends of the nascent H strand and L strand, the resulting single-stranded gaps are ligated by the mitochondrial isoform of ligase III (LIG3 isoform 1) (Lakshmipathy and Campbell 1999, 2001, Ruhanen et al. 2011, demonstrated in vitro in Karlowicz et al. 2022, inferred from mouse cells in Simsek et al. 2011). Only the catalytic core of LIG3-1 is required and a minimal viral ligase can substitute for LIG3-1 (inferred from mouse cells in Simsek et al. 2011). LIG3-1 interacts with the POLG subunit of DNA polymerase gamma (POLG:POLG2) via the zinc finger domain of LIG3-1 and this interaction increases the recruitment of POLG:POLG2 to single-stranded breaks (De and Campbell 2007). Knockdown of LIG3-1 in human cells results in replication intermediates with increased numbers of single-strand breaks (Ruhanen et al. 2011). In mice, Lig3 is required for mitochondrial DNA integrity (Gao et al. 2011).
Literature References
PubMed ID Title Journal Year
17054425 A novel interaction between DNA ligase III and DNA polymerase gamma plays an essential role in mitochondrial DNA stability

De, A, Campbell, C

Biochem J 2007
35819194 In vitro reconstitution reveals a key role of human mitochondrial EXOG in RNA primer processing

Karlowicz, A, Dubiel, AB, Czerwinska, J, Bledea, A, Purzycki, P, Grzelewska, M, McAuley, RJ, Szczesny, RJ, Brzuska, G, Krol, E, Szczesny, B, Szymanski, MR

Nucleic Acids Res 2022
28751376 Kinetic analyses of single-stranded break repair by human DNA ligase III isoforms reveal biochemical differences from DNA ligase I

McNally, JR, O'Brien, PJ

J Biol Chem 2017
20518483 Human DNA ligase III recognizes DNA ends by dynamic switching between two DNA-bound states

Cotner-Gohara, E, Kim, IK, Hammel, M, Tainer, JA, Tomkinson, AE, Ellenberger, T

Biochemistry 2010
11160888 Antisense-mediated decrease in DNA ligase III expression results in reduced mitochondrial DNA integrity

Lakshmipathy, U, Campbell, C

Nucleic Acids Res 2001
26130724 Human DNA ligase III bridges two DNA ends to promote specific intermolecular DNA end joining

Kukshal, V, Kim, IK, Hura, GL, Tomkinson, AE, Tainer, JA, Ellenberger, T

Nucleic Acids Res 2015
21878356 Involvement of DNA ligase III and ribonuclease H1 in mitochondrial DNA replication in cultured human cells

Ruhanen, H, Ushakov, K, Yasukawa, T

Biochim Biophys Acta 2011
10207110 The human DNA ligase III gene encodes nuclear and mitochondrial proteins

Lakshmipathy, U, Campbell, C

Mol Cell Biol 1999
Participants
Input
Output
Participates
as an event of
Catalyst Activity

DNA ligase (ATP) activity of LIG3-1:Mg2+ [mitochondrial matrix]

Physical Entity
LIG3-1:Mg2+ [mitochondrial matrix] (Homo sapiens)
Activity
DNA ligase (ATP) activity (GO:0003910)
Authored
May, B  (2024-06-29)
Reviewed
Wu, CC  (2024-10-27)
Created
May, B  (2024-06-30)
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