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FLASH GENE

Symbol

LIG3

contributors: mct/npt - updated : 01-10-2015

HGNC name	ligase III, DNA, ATP-dependent
HGNC id	6600

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	24.57 kb     20 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002311 20 - 3103 NP_002302 102 949 found in the nucleus and the mitochondria 2013 2401308 variant (beta) germ line-specific splicing isoform NM_013975 20 - 3722 NP_039269 108.7 1009 ubiquitous, found in the nucleus and the mitochondria 2013 2401308 variant (alpha) functional redundancy between DNA ligase III alpha and DNA ligase I in excision repair essential for DNA replication in the absence of the replicative DNA ligase, DNA ligase I is a component of an alternative non-homologous end joining (NHEJ) pathway for DNA double-strand break (DSB) repair

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Reproductive female system uterus cervix   highly   male system testis     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a BRCT domain
	a PARP-type zinc finger

HOMOLOGY

Homologene

FAMILY

DNA ligase family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
	intracellular,nucleus,nucleoplasm
	intracellular,nucleus,chromatin/chromosome
text	present in the mitochondria, where its role in mitochondrial DNA (mtDNA) maintenance is independent of XRCC1

basic FUNCTION	can correct defective DNA strand-break repair
	and sister chromatid exchange following treatment with ionizing radiation and alkylating agents
	required for microhomology-mediated end joining of DNA double-strand breaks
	critical biological role of LIG3 is to maintain mtDNA integrity and not XRCC1-dependent DNA repair
	LIG3 function was central to mitochondrial DNA maintenance 0)
	promotes alternative nonhomologous end-joining during chromosomal translocation formation
	crucial for cell survival due to its catalytic function in mitochondria
	restricted to higher eukaryotes and has been associated with base excision (BER) and single strand break repair (SSBR)
	XRCC1, a LIG3-stabilizing cofactor, and LIG3 itself have been very widely assumed to provide major end-ligation functions in A-EJ (alternative end-joining)
	remarkable ability for LIG3 to backup DSB repair by NHEJ in addition to its essential function in the mitochondria
	LIG1 and LIG3 cooperate in alternative non-homologous end-joining
	LIG1 is not absolutely required for cellular DNA replication and repair and either LIG3 or LIG4 can substitute for the role of LIG1 in joining Okazaki fragments
	LIG3 isoforms were seven times more efficient than LIG1 at ligating nicked DNA under optimal conditions

CELLULAR PROCESS	nucleotide, replication
	nucleotide, repair, recombination

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

complexing with XRCC1

INTERACTION

DNA

RNA

small molecule

protein	interacts with DNA-repair protein XRCC1 (translocation of XRCC1 with LIG3 from centrosomes to chromosomes in response to DNA damage in mitotic cells)
	LIG1 was critical for DNA repair, but acted in a cooperative manner with LIG3
	interacting with POLG (interaction of DNA ligase III and DNA polymerase gamma is required for proper maintenance of the mitochondrial genome)
	functional flexibility and interchangeability between LIG1 and LIG3
	DNA repair partners of TDP1 include PARP1, XRCC1, ligase III and PNKP from the base excision repair (BER) pathway

cell & other

REGULATION

ASSOCIATED DISORDERS

ANIMAL & CELL MODELS