LIG4

DNA ligase 4 is an enzyme that in

humans is encoded by the LIG4
LIG4
gene.[5]

Contents
Function
LIG4 Syndrome
Available structures
Haematopoietic stem cell PDB Ortholog search: PDBe (https://www.ebi.ac.uk/pdbe/search
aging
Results.html?display=both&term=Q8BTF7%20or%20P4991
Interactions 7) RCSB (http://www.rcsb.org/pdb/search/smartSubquery.d
Mechanism o?smartSearchSubtype=UpAccessionIdQuery&accessionId
References List=Q8BTF7,P49917)

Further reading List of PDB id codes

1IK9 (https://www.rcsb.org/structure/1IK9), 2E2W (htt

Function
The protein encoded by this gene is
an ATP-dependent DNA ligase that
joins double-strand breaks during the
non-homologous end joining
pathway of double-strand break
repair. It is also essential for V(D)J
recombination. Lig4 forms a
complex with XRCC4, and further
interacts with the DNA-dependent
protein kinase (DNA-PK) and
XLF/Cernunnos, which are also
required for NHEJ. The crystal
structure of the Lig4/XRCC4
complex has been resolved.[6]
Defects in this gene are the cause of
LIG4 syndrome. The yeast homolog
of Lig4 is Dnl4.
ps://www.rcsb.org/structure/2E2W), 3II6 (https://www.
rcsb.org/structure/3II6), 3VNN (https://www.rcsb.org/
structure/3VNN), 3W1B (https://www.rcsb.org/structu
re/3W1B), 3W1G (https://www.rcsb.org/structure/3W
1G), 3W5O (https://www.rcsb.org/structure/3W5O),
4HTO (https://www.rcsb.org/structure/4HTO), 4HTP
(https://www.rcsb.org/structure/4HTP)
Identifiers
Aliases LIG4 (https://www.genenames.org/data/gene-symbol-rep
ort/#!/hgnc_id/6601), LIG4S, DNA ligase 4
External OMIM: 601837 (https://omim.org/entry/601837) MGI:
IDs 1335098 (http://www.informatics.jax.org/marker/MGI:133
5098) HomoloGene: 1736 (https://www.ncbi.nlm.nih.gov/
entrez/query.fcgi?cmd=Retrieve&db=homologene&dopt=
HomoloGene&list_uids=1736) GeneCards: LIG4 (https://
www.genecards.org/cgi-bin/carddisp.pl?gene=LIG4)
Gene location (Human)

LIG4 Syndrome
In humans, deficiency of DNA ligase
4 results in a clinical condition
known as LIG4 syndrome. This
syndrome is characterized by cellular
radiation sensitivity, growth Chr. Chromosome 13 (human)[1]
retardation, developmental delay,
microcephaly, facial dysmorphisms,
increased disposition to leukemia,
variable degrees of
Band 13q33.3 Start 108,207,439 bp[1]
immunodeficiency and reduced
number of blood cells.[7][8] End 108,218,368 bp[1]

Gene location (Mouse)

Haematopoietic stem
cell aging
Accumulation of DNA damage
leading to stem cell exhaustion is
regarded as an important aspect of
Chr. Chromosome 8 (mouse)[2]
aging.[9][10] Deficiency of lig4 in
pluripotent stem cells impairs Non-
homologous end joining (NHEJ) and
results in accumulation of DNA
double-strand breaks and enhanced Band 8|8 A1.1 Start 9,969,049 bp[2]
apoptosis.[8] Lig4 deficiency in the End 9,977,686 bp[2]
mouse causes a progressive loss of
haematopoietic stem cells and bone RNA expression pattern
marrow cellularity during aging.[11]
The sensitivity of haematopoietic
stem cells to lig4 deficiency suggests
that lig4-mediated NHEJ is a key
determinant of the ability of stem
cells to maintain themselves against
physiological stress over time.[8][11]

Interactions
LIG4 has been shown to interact
with XRCC4 via its BRCT
domain.[12][6] This interaction
stabilizes LIG4 protein in cells; cells
that are deficient for XRCC4, such
as XR-1 cells, have reduced levels of
LIG4.[13]
Mechanism
LIG4 is an ATP-dependent DNA
ligase. LIG4 uses ATP to adenylate
itself and then transfers the AMP
group to the 5' phosphate of one
DNA end. Nucleophilic attack by the
3' hydroxyl group of a second DNA
end and release of AMP yield the
More reference expression data (http://biogps.org/gene/3981/)
Gene ontology
Molecular • nucleotide binding (http://amigo.geneontology.org/a
function migo/term/GO:0000166)
• metal ion binding (http://amigo.geneontology.org/ami
go/term/GO:0046872)
• protein C-terminus binding (http://amigo.geneontolo
gy.org/amigo/term/GO:0008022)
• GO:0001948 protein binding (http://amigo.geneontol
ogy.org/amigo/term/GO:0005515,)
• ATP binding (http://amigo.geneontology.org/amigo/te
rm/GO:0005524)
• DNA ligase (ATP) activity (http://amigo.geneontology.
org/amigo/term/GO:0003910)
• ligase activity (http://amigo.geneontology.org/amigo/t
erm/GO:0016874)
ligation product. Adenylation of
LIG4 is stimulated by XRCC4 and
XLF.[14]
References
1. GRCh38: Ensembl release
89: ENSG00000174405 (htt
p://May2017.archive.ensemb
l.org/Homo_sapiens/Gene/Su
mmary?db=core;g=ENSG000
00174405) - Ensembl, May
2017
2. GRCm38: Ensembl release
89: ENSMUSG00000049717
(http://May2017.archive.ense
mbl.org/Mus_musculus/Gene/
Summary?db=core;g=ENSM
USG00000049717) -
Ensembl, May 2017
3. "Human PubMed Reference:"
(https://www.ncbi.nlm.nih.gov/
sites/entrez?db=gene&cmd=
Link&LinkName=gene_pubm
ed&from_uid=3981). National
Center for Biotechnology
Information, U.S. National
Library of Medicine.
4. "Mouse PubMed Reference:"
(https://www.ncbi.nlm.nih.gov/
sites/entrez?db=gene&cmd=
Link&LinkName=gene_pubm
ed&from_uid=319583).
National Center for
Biotechnology Information,
U.S. National Library of
Medicine.
5. "Entrez Gene: LIG4 ligase IV,
DNA, ATP-dependent" (http
s://www.ncbi.nlm.nih.gov/site
s/entrez?Db=gene&Cmd=Sh
owDetailView&TermToSearc
h=3981).
• DNA binding (http://amigo.geneontology.org/amigo/t
erm/GO:0003677)
• DNA ligase activity (http://amigo.geneontology.org/a
migo/term/GO:0003909)
Cellular • nucleoplasm (http://amigo.geneontology.org/amigo/t
component erm/GO:0005654)
• DNA ligase IV complex (http://amigo.geneontology.or
g/amigo/term/GO:0032807)
• nonhomologous end joining complex (http://amigo.g
eneontology.org/amigo/term/GO:0070419)
• condensed chromosome (http://amigo.geneontology.
org/amigo/term/GO:0000793)
• nuclear chromosome, telomeric region (http://amigo.
geneontology.org/amigo/term/GO:0000784)
• cell nucleus (http://amigo.geneontology.org/amigo/te
rm/GO:0005634)
• DNA-dependent protein kinase-DNA ligase 4
complex (http://amigo.geneontology.org/amigo/term/G
O:0005958)
• cytoplasm (http://amigo.geneontology.org/amigo/ter
m/GO:0005737)
• cytoplasmic ribonucleoprotein granule (http://amigo.
geneontology.org/amigo/term/GO:0036464)
Biological • nucleotide-excision repair, DNA gap filling (http://ami
process go.geneontology.org/amigo/term/GO:0006297)
• double-strand break repair via classical
nonhomologous end joining (http://amigo.geneontolog
y.org/amigo/term/GO:0097680)
• response to ionizing radiation (http://amigo.geneonto
logy.org/amigo/term/GO:0010212)
• DNA recombination (http://amigo.geneontology.org/a
migo/term/GO:0006310)
• lagging strand elongation (http://amigo.geneontolog
y.org/amigo/term/GO:0006273)
• DNA biosynthetic process (http://amigo.geneontolog
y.org/amigo/term/GO:0071897)
• cellular response to lithium ion (http://amigo.geneont
ology.org/amigo/term/GO:0071285)
• single strand break repair (http://amigo.geneontolog
y.org/amigo/term/GO:0000012)
• cellular response to DNA damage stimulus (http://am
igo.geneontology.org/amigo/term/GO:0006974)
• cell division (http://amigo.geneontology.org/amigo/ter
m/GO:0051301)
• DNA replication (http://amigo.geneontology.org/amig
o/term/GO:0006260)
6. Sibanda BL, Critchlow SE,
Begun J, Pei XY, Jackson SP,
Blundell TL, Pellegrini L
(December 2001). "Crystal
structure of an Xrcc4-DNA
ligase IV complex". Nature
Structural Biology. 8 (12):
1015–9. doi:10.1038/nsb725
(https://doi.org/10.1038%2Fn
sb725). PMID 11702069 (http
s://pubmed.ncbi.nlm.nih.gov/1
1702069).
7. Rucci F, Notarangelo LD,
Fazeli A, Patrizi L, Hickernell
T, Paganini T, Coakley KM,
Detre C, Keszei M, Walter JE,
Feldman L, Cheng HL,
Poliani PL, Wang JH, Balter
BB, Recher M, Andersson
EM, Zha S, Giliani S, Terhorst
C, Alt FW, Yan CT (February
2010). "Homozygous DNA
ligase IV R278H mutation in
mice leads to leaky SCID and
represents a model for human
LIG4 syndrome" (https://www.
ncbi.nlm.nih.gov/pmc/articles/
PMC2840307). Proceedings
of the National Academy of
Sciences of the United States
of America. 107 (7): 3024–9.
doi:10.1073/pnas.091486510
7 (https://doi.org/10.1073%2F
pnas.0914865107).
PMC 2840307 (https://www.n
cbi.nlm.nih.gov/pmc/articles/P
MC2840307).
PMID 20133615 (https://pubm
ed.ncbi.nlm.nih.gov/2013361
5).
• GO:1903310 positive regulation of chromosome
organization (http://amigo.geneontology.org/amigo/ter
m/GO:2001252,)
• establishment of integrated proviral latency (http://a
migo.geneontology.org/amigo/term/GO:0075713)
• cell cycle (http://amigo.geneontology.org/amigo/ter
m/GO:0007049)
• response to X-ray (http://amigo.geneontology.org/a
migo/term/GO:0010165)
• positive regulation of neurogenesis (http://amigo.gen
eontology.org/amigo/term/GO:0050769)
• DNA ligation involved in DNA recombination (http://a
migo.geneontology.org/amigo/term/GO:0051102)
• DNA ligation (http://amigo.geneontology.org/amigo/t
erm/GO:0006266)
• DNA ligation involved in DNA repair (http://amigo.ge
neontology.org/amigo/term/GO:0051103)
• somatic stem cell population maintenance (http://ami
go.geneontology.org/amigo/term/GO:0035019)
• chromosome organization (http://amigo.geneontolog
y.org/amigo/term/GO:0051276)
• T cell receptor V(D)J recombination (http://amigo.ge
neontology.org/amigo/term/GO:0033153)
• neuron apoptotic process (http://amigo.geneontolog
y.org/amigo/term/GO:0051402)
• isotype switching (http://amigo.geneontology.org/ami
go/term/GO:0045190)
• T cell differentiation in thymus (http://amigo.geneont
ology.org/amigo/term/GO:0033077)
• central nervous system development (http://amigo.g
eneontology.org/amigo/term/GO:0007417)
• immunoglobulin V(D)J recombination (http://amigo.g
eneontology.org/amigo/term/GO:0033152)
• double-strand break repair via nonhomologous end
joining (http://amigo.geneontology.org/amigo/term/G
O:0006303)
• positive regulation of fibroblast proliferation (http://a
migo.geneontology.org/amigo/term/GO:0048146)
• in utero embryonic development (http://amigo.geneo
ntology.org/amigo/term/GO:0001701)
• cellular proliferation (http://amigo.geneontology.org/a
migo/term/GO:0008283)
• V(D)J recombination (http://amigo.geneontology.org/
amigo/term/GO:0033151)
• pro-B cell differentiation (http://amigo.geneontology.
org/amigo/term/GO:0002328)
 8. Tilgner K, Neganova I,
Moreno-Gimeno I, Al-Aama
JY, Burks D, Yung S,
Singhapol C, Saretzki G,
Evans J, Gorbunova V,
Gennery A, Przyborski S,
Stojkovic M, Armstrong L,
Jeggo P, Lako M (August
2013). "A human iPSC model
of Ligase IV deficiency
reveals an important role for
NHEJ-mediated-DSB repair
in the survival and genomic
stability of induced pluripotent
stem cells and emerging
haematopoietic progenitors"
(https://www.ncbi.nlm.nih.gov/
pmc/articles/PMC3705601).
Cell Death and
Differentiation. 20 (8): 1089–
100. doi:10.1038/cdd.2013.44
(https://doi.org/10.1038%2Fc
dd.2013.44). PMC 3705601
(https://www.ncbi.nlm.nih.gov/
pmc/articles/PMC3705601).
PMID 23722522 (https://pubm
ed.ncbi.nlm.nih.gov/2372252
2).
9. Rossi DJ, Bryder D, Seita J,
Nussenzweig A, Hoeijmakers
J, Weissman IL (June 2007).
"Deficiencies in DNA
damage repair limit the
function of haematopoietic
stem cells with age". Nature.
447 (7145): 725–9.
doi:10.1038/nature05862 (htt
ps://doi.org/10.1038%2Fnatur
e05862). PMID 17554309 (htt
ps://pubmed.ncbi.nlm.nih.gov/
17554309).
10. Bernstein H, Payne CM,
Bernstein C, Garewal H,
Dvorak K (2008). "Chapter 1:
Cancer and aging as
consequences of un-repaired
DNA damage" (https://www.n
ovapublishers.com/catalog/pr
oduct_info.php?products_id=
43247). In Kimura H, Suzuki
A (eds.). New Research on
DNA Damages. New York:
Nova Science Publishers,
Inc. pp. 1–47. ISBN 978-1-
60456-581-2.
• DNA repair (http://amigo.geneontology.org/amigo/ter
m/GO:0006281)
• response to gamma radiation (http://amigo.geneonto
logy.org/amigo/term/GO:0010332)
• double-strand break repair (http://amigo.geneontolo
gy.org/amigo/term/GO:0006302)
• negative regulation of neuron apoptotic process (htt
p://amigo.geneontology.org/amigo/term/GO:0043524)
• cellular response to ionizing radiation (http://amigo.g
eneontology.org/amigo/term/GO:0071479)
Sources:Amigo (http://amigo.geneontology.org/) / QuickGO (https://
www.ebi.ac.uk/QuickGO/)
Orthologs
Species Human Mouse
Entrez
3981 (https://www.ncb 319583 (https://www.ncb
i.nlm.nih.gov/entrez/qu i.nlm.nih.gov/entrez/quer
ery.fcgi?db=gene&cm y.fcgi?db=gene&cmd=retr
d=retrieve&dopt=defa ieve&dopt=default&list_u
ult&list_uids=3981&rn ids=319583&rn=1)
=1)
Ensembl
ENSG00000174405 ENSMUSG00000049717
(http://www.ensembl.o (http://www.ensembl.org/
rg/Homo_sapiens/gen Mus_musculus/genevie
eview?gene=ENSG00 w?gene=ENSMUSG000
000174405;db=core) 00049717;db=core)
UniProt
P49917 (https://www.u Q8BTF7 (https://www.uni
niprot.org/uniprot/P49 prot.org/uniprot/Q8BTF7)
917)
RefSeq NM_001098268 (https://
(mRNA) www.ncbi.nlm.nih.gov/ NM_176953 (https://ww
entrez/viewer.fcgi?val= w.ncbi.nlm.nih.gov/entre
z/viewer.fcgi?val=NM_17
NM_001098268)
NM_002312 (https://ww 6953)
NM_001377042 (https://
w.ncbi.nlm.nih.gov/entr
www.ncbi.nlm.nih.gov/ent
ez/viewer.fcgi?val=NM_
rez/viewer.fcgi?val=NM_
002312)
001377042)
NM_206937 (https://ww
w.ncbi.nlm.nih.gov/entr
ez/viewer.fcgi?val=NM_
206937)
11. Nijnik A, Woodbine L,
Marchetti C, Dawson S,
Lambe T, Liu C, Rodrigues
NP, Crockford TL, Cabuy E,
Vindigni A, Enver T, Bell JI,
Slijepcevic P, Goodnow CC,
Jeggo PA, Cornall RJ (June
2007). "DNA repair is limiting
for haematopoietic stem cells
during ageing". Nature. 447
(7145): 686–90.
doi:10.1038/nature05875 (htt
ps://doi.org/10.1038%2Fnatur
e05875). PMID 17554302 (htt
ps://pubmed.ncbi.nlm.nih.gov/
17554302).
12. Deshpande RA, Wilson TE
(October 2007). "Modes of
interaction among yeast Nej1,
Lif1 and Dnl4 proteins and
comparison to human XLF,
XRCC4 and Lig4" (https://ww
w.ncbi.nlm.nih.gov/pmc/articl
es/PMC2064958). DNA
Repair. 6 (10): 1507–16.
doi:10.1016/j.dnarep.2007.04
.014 (https://doi.org/10.1016%
2Fj.dnarep.2007.04.014).
PMC 2064958 (https://www.n
cbi.nlm.nih.gov/pmc/articles/P
MC2064958).
PMID 17567543 (https://pubm
ed.ncbi.nlm.nih.gov/1756754
3).
13. Bryans M, Valenzano MC,
Stamato TD (January 1999).
"Absence of DNA ligase IV
protein in XR-1 cells:
evidence for stabilization by
XRCC4". Mutation Research.
433 (1): 53–8.
doi:10.1016/s0921-
8777(98)00063-9 (https://doi.
org/10.1016%2Fs0921-877
7%2898%2900063-9).
PMID 10047779 (https://pubm
ed.ncbi.nlm.nih.gov/1004777
9).
NM_001330595 (https://
www.ncbi.nlm.nih.gov/
entrez/viewer.fcgi?val=
NM_001330595)
NM_001352598 (https://
www.ncbi.nlm.nih.gov/
entrez/viewer.fcgi?val=
NM_001352598)
NM_001352599 (http
s://www.ncbi.nlm.nih.g
ov/entrez/viewer.fcgi?
val=NM_001352599)
NM_001352600 (http
s://www.ncbi.nlm.nih.g
ov/entrez/viewer.fcgi?
val=NM_001352600)
NM_001352601 (http
s://www.ncbi.nlm.nih.g
ov/entrez/viewer.fcgi?
val=NM_001352601)
NM_001352602 (http
s://www.ncbi.nlm.nih.g
ov/entrez/viewer.fcgi?
val=NM_001352602)
NM_001352603 (http
s://www.ncbi.nlm.nih.g
ov/entrez/viewer.fcgi?
val=NM_001352603)
NM_001352604 (http
s://www.ncbi.nlm.nih.g
ov/entrez/viewer.fcgi?
val=NM_001352604)
NM_001379095 (http
s://www.ncbi.nlm.nih.g
ov/entrez/viewer.fcgi?
val=NM_001379095)
RefSeq NP_001091738 (https://
(protein) www.ncbi.nlm.nih.gov/ NP_795927 (https://www.
entrez/viewer.fcgi?val= ncbi.nlm.nih.gov/entrez/vi
ewer.fcgi?val=NP_79592
NP_001091738)
7)
NP_001317524 (https://
NP_001363971 (https://w
www.ncbi.nlm.nih.gov/
ww.ncbi.nlm.nih.gov/entr
entrez/viewer.fcgi?val=
ez/viewer.fcgi?val=NP_0
NP_001317524) 01363971)
NP_002303 (https://ww
w.ncbi.nlm.nih.gov/entr
ez/viewer.fcgi?val=NP_
002303)
14. Mahaney BL, Hammel M,
Meek K, Tainer JA, Lees-
Miller SP (February 2013).
"XRCC4 and XLF form long
helical protein filaments
suitable for DNA end
protection and alignment to
facilitate DNA double strand
break repair" (https://www.ncb
i.nlm.nih.gov/pmc/articles/PM
C3725335). Biochemistry and
Cell Biology. 91 (1): 31–41.
doi:10.1139/bcb-2012-0058
(https://doi.org/10.1139%2Fb
cb-2012-0058).
PMC 3725335 (https://www.n
cbi.nlm.nih.gov/pmc/articles/P
MC3725335).
PMID 23442139 (https://pubm
ed.ncbi.nlm.nih.gov/2344213
9).
Further reading
Wei YF, Robins P, Carter K,
Caldecott K, Pappin DJ, Yu
GL, Wang RP, Shell BK,
Nash RA, Schär P (June
1995). "Molecular cloning
and expression of human
cDNAs encoding a novel
DNA ligase IV and DNA
ligase III, an enzyme active in
DNA repair and
recombination" (https://www.n
cbi.nlm.nih.gov/pmc/articles/P
MC230553). Molecular and
Cellular Biology. 15 (6):
3206–16.
doi:10.1128/mcb.15.6.3206 (h
ttps://doi.org/10.1128%2Fmc
b.15.6.3206). PMC 230553 (h
ttps://www.ncbi.nlm.nih.gov/p
mc/articles/PMC230553).
PMID 7760816 (https://pubme
d.ncbi.nlm.nih.gov/7760816).
NP_996820 (https://ww
w.ncbi.nlm.nih.gov/entr
ez/viewer.fcgi?val=NP_
996820)
NP_001339527 (https://
www.ncbi.nlm.nih.gov/
entrez/viewer.fcgi?val=
NP_001339527)
NP_001339528 (http
s://www.ncbi.nlm.nih.g
ov/entrez/viewer.fcgi?
val=NP_001339528)
NP_001339529 (http
s://www.ncbi.nlm.nih.g
ov/entrez/viewer.fcgi?
val=NP_001339529)
NP_001339530 (http
s://www.ncbi.nlm.nih.g
ov/entrez/viewer.fcgi?
val=NP_001339530)
NP_001339531 (http
s://www.ncbi.nlm.nih.g
ov/entrez/viewer.fcgi?
val=NP_001339531)
NP_001339532 (http
s://www.ncbi.nlm.nih.g
ov/entrez/viewer.fcgi?
val=NP_001339532)
NP_001339533 (http
s://www.ncbi.nlm.nih.g
ov/entrez/viewer.fcgi?
val=NP_001339533)
NP_001366024 (http
s://www.ncbi.nlm.nih.g
ov/entrez/viewer.fcgi?
val=NP_001366024)
Location Chr 13: 108.21 – 108.22 Chr 8: 9.97 – 9.98 Mb (http
(UCSC) Mb (https://genome.ucsc. s://genome.ucsc.edu/cgi-bin/
edu/cgi-bin/hgTracks?org hgTracks?org=Mouse&db=m
=Human&db=hg38&positi m0&position=chr8:9969049-9
on=chr13:108207439-108 977686)
218368)
PubMed [3] [4]
search
Wikidata
View/Edit Human View/Edit Mouse
Robins P, Lindahl T
(September 1996). "DNA
ligase IV from HeLa cell
nuclei" (https://doi.org/10.107
4/jbc.271.39.24257). The
Journal of Biological
Chemistry. 271 (39): 24257–
61.
doi:10.1074/jbc.271.39.24257
(https://doi.org/10.1074%2Fjb
c.271.39.24257).
PMID 8798671 (https://pubme
d.ncbi.nlm.nih.gov/8798671).
Grawunder U, Wilm M, Wu X,
Kulesza P, Wilson TE, Mann
M, Lieber MR (July 1997).
"Activity of DNA ligase IV
stimulated by complex
formation with XRCC4
protein in mammalian cells".
Nature. 388 (6641): 492–5.
doi:10.1038/41358 (https://do
i.org/10.1038%2F41358).
PMID 9242410 (https://pubme
d.ncbi.nlm.nih.gov/9242410).
Critchlow SE, Bowater RP,
Jackson SP (August 1997).
"Mammalian DNA double-
strand break repair protein
XRCC4 interacts with DNA
ligase IV" (https://doi.org/10.1
016/S0960-9822(06)00258-
2). Current Biology. 7 (8):
588–98. doi:10.1016/S0960-
9822(06)00258-2 (https://doi.
org/10.1016%2FS0960-982
2%2806%2900258-2).
PMID 9259561 (https://pubme
d.ncbi.nlm.nih.gov/9259561).
Grawunder U, Zimmer D,
Lieber MR (July 1998). "DNA
ligase IV binds to XRCC4 via
a motif located between
rather than within its BRCT
domains". Current Biology. 8
(15): 873–6.
doi:10.1016/S0960-
9822(07)00349-1 (https://doi.
org/10.1016%2FS0960-982
2%2807%2900349-1).
PMID 9705934 (https://pubme
d.ncbi.nlm.nih.gov/9705934).
Grawunder U, Zimmer D,
Fugmann S, Schwarz K,
Lieber MR (October 1998).
"DNA ligase IV is essential
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