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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
1994-1-21
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pubmed:abstractText |
Two missense mutations in different alleles of the DNA ligase I gene have been described in a patient (46BR) with immunodeficiencies and cellular hypersensitivity to DNA-damaging agents. One of the mutant alleles produces an inactive protein, while the other encodes an enzyme with some residual activity. A subline of identical phenotype that is homozygous (or hemizygous) for the mutant allele encoding this partially active enzyme has facilitated characterization of the enzymatic defect in 46BR. This subline retains only 3 to 5% of normal DNA ligase I activity. The intermediates in the ligation reaction, DNA ligase I-AMP and nicked DNA-AMP, accumulate in vitro and in vivo. The defect of the 46BR enzyme lies primarily in conversion of nicked DNA-AMP into the final ligated DNA product. Assays of DNA repair in 46BR cell extracts and of DNA replication in permeabilized cells have clarified functional roles of DNA ligase I. The initial rate of ligation of Okazaki fragments during DNA replication is apparently normal in 46BR cells, but 25 to 30% of the fragments remain in low-molecular-weight form for prolonged times. DNA base excision repair by 46BR cell extracts shows a delay in ligation and an anomalously long repair patch size that is reduced upon addition of purified normal DNA ligase I.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-1351188,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-1497311,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-1549115,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-1549180,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-1549587,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-1569068,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-1581963,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-1639065,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-1671570,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-1695631,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-1939197,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-2169868,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-2197279,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-2204063,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-227871,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-2363731,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-2393905,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-2498001,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-3002824,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-3180052,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-3349527,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-3856882,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-4353283,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-4353284,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-4377758,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-4922293,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-6193397,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-6253446,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-6313714,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-6850987,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-6850988,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-7680646,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-7683758,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8264597-8392066
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0270-7306
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
14
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
310-7
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:8264597-Adenosine Monophosphate,
pubmed-meshheading:8264597-Base Sequence,
pubmed-meshheading:8264597-Cell Line,
pubmed-meshheading:8264597-DNA,
pubmed-meshheading:8264597-DNA Ligases,
pubmed-meshheading:8264597-DNA Repair,
pubmed-meshheading:8264597-DNA Replication,
pubmed-meshheading:8264597-Genetic Complementation Test,
pubmed-meshheading:8264597-Humans,
pubmed-meshheading:8264597-Immunologic Deficiency Syndromes,
pubmed-meshheading:8264597-Molecular Sequence Data,
pubmed-meshheading:8264597-Mutation
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pubmed:year |
1994
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pubmed:articleTitle |
Aberrant DNA repair and DNA replication due to an inherited enzymatic defect in human DNA ligase I.
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pubmed:affiliation |
Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Hertfordshire, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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