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Title: Hypomutability in Fanconi anemia cells is associated with increased deletion frequency at the HPRT locus

Abstract

Fanconi anemia (FA) is an inherited human disorder associated with a predisposition to cancer and characterized by anomalies in the processing of DNA cross-links and certain monoadducts. The authors reported previously that the frequency of psoralen-photoinduced mutations at the HPRT locus is lower in FA cells than in normal cells. This hypomutability is shown here to be associated with an increased frequency of deletions in the HPRT gene when either a mixture of cross-links and monoadducts or monoadducts alone are induced. Molecular analysis of mutants in the HPRT gene was carried out. In normal cells the majority of spontaneous and induced mutants are point mutations whereas in FA deletion mutations predominate. In that case a majority of mutants were found to lack individual exons or small clusters of exons whereas in normal cells large (complete or major gene loss) and small deletions are almost equally represented. Thus they propose that the FA defect lies in a mutagenic pathway that, in normal cells, involves by passing lesions and subsequent gap filling by a recombinational process during replication.

Authors:
; ;  [1];  [2]
  1. Unite Recherche Associee due Centre National del La Recherche Scientifique, Paris (France)
  2. Lawrence Livermore National Lab., CA (United States)
Publication Date:
OSTI Identifier:
5534082
Resource Type:
Journal Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America; (United States)
Additional Journal Information:
Journal Volume: 87:21; Journal ID: ISSN 0027-8424
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; HEREDITARY DISEASES; DNA REPAIR; HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE; GENE MUTATIONS; ANEMIAS; DNA ADDUCTS; DNA HYBRIDIZATION; LYMPHOCYTES; MAN; MUTATION FREQUENCY; PHOSPHORUS 32; PSORALEN; ADDUCTS; ANIMAL CELLS; ANIMALS; ANTICOAGULANTS; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BIOLOGICAL MATERIALS; BIOLOGICAL RECOVERY; BIOLOGICAL REPAIR; BLOOD; BLOOD CELLS; BODY FLUIDS; CONNECTIVE TISSUE CELLS; COUMARINS; DAYS LIVING RADIOISOTOPES; DISEASES; DRUGS; ENZYMES; GLYCOSYL TRANSFERASES; HEMATOLOGIC AGENTS; HEMIC DISEASES; HETEROCYCLIC COMPOUNDS; HYBRIDIZATION; ISOTOPES; LEUKOCYTES; LIGHT NUCLEI; MAMMALS; MATERIALS; MUTATIONS; NUCLEI; ODD-ODD NUCLEI; ORGANIC COMPOUNDS; ORGANIC OXYGEN COMPOUNDS; PENTOSYL TRANSFERASES; PHOSPHORUS ISOTOPES; PRIMATES; PROTEINS; RADIOISOTOPES; RECOVERY; REPAIR; SOMATIC CELLS; SYMPTOMS; TRANSFERASES; VERTEBRATES; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Papadopoulo, D, Guillouf, C, Moustacchi, E, and Mohrenweiser, H. Hypomutability in Fanconi anemia cells is associated with increased deletion frequency at the HPRT locus. United States: N. p., 1990. Web. doi:10.1073/pnas.87.21.8383.
Papadopoulo, D, Guillouf, C, Moustacchi, E, & Mohrenweiser, H. Hypomutability in Fanconi anemia cells is associated with increased deletion frequency at the HPRT locus. United States. doi:10.1073/pnas.87.21.8383.
Papadopoulo, D, Guillouf, C, Moustacchi, E, and Mohrenweiser, H. Thu . "Hypomutability in Fanconi anemia cells is associated with increased deletion frequency at the HPRT locus". United States. doi:10.1073/pnas.87.21.8383.
@article{osti_5534082,
title = {Hypomutability in Fanconi anemia cells is associated with increased deletion frequency at the HPRT locus},
author = {Papadopoulo, D and Guillouf, C and Moustacchi, E and Mohrenweiser, H},
abstractNote = {Fanconi anemia (FA) is an inherited human disorder associated with a predisposition to cancer and characterized by anomalies in the processing of DNA cross-links and certain monoadducts. The authors reported previously that the frequency of psoralen-photoinduced mutations at the HPRT locus is lower in FA cells than in normal cells. This hypomutability is shown here to be associated with an increased frequency of deletions in the HPRT gene when either a mixture of cross-links and monoadducts or monoadducts alone are induced. Molecular analysis of mutants in the HPRT gene was carried out. In normal cells the majority of spontaneous and induced mutants are point mutations whereas in FA deletion mutations predominate. In that case a majority of mutants were found to lack individual exons or small clusters of exons whereas in normal cells large (complete or major gene loss) and small deletions are almost equally represented. Thus they propose that the FA defect lies in a mutagenic pathway that, in normal cells, involves by passing lesions and subsequent gap filling by a recombinational process during replication.},
doi = {10.1073/pnas.87.21.8383},
journal = {Proceedings of the National Academy of Sciences of the United States of America; (United States)},
issn = {0027-8424},
number = ,
volume = 87:21,
place = {United States},
year = {1990},
month = {11}
}