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B lymphocytes of xeroderma pigmentosum or Cockayne syndrome patients with inherited defects in nucleotide excision repair are fully capable of somatic hypermutation of immunoglobulin genes.

Kim N, Kage K, Matsuda F, Lefranc MP, Storb U - J. Exp. Med. (1997)

Bottom Line: This suggests that these B cells can undergo somatic hypermutation despite significant defects in NER.Thus, it is doubtful that NER is an essential part of the mechanism of somatic hypermutation of Ig genes.As an aside, NER seems also not involved in Ig gene switch recombination.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Chicago, Illinois 60637, USA.

ABSTRACT
Recent experiments have strongly suggested that the process of somatic mutation is linked to transcription initiation. It was postulated that a mutator factor loads onto the RNA polymerase and, during elongation, causes transcriptional arrest that activates DNA repair, thus occasionally causing errors in the DNA sequence. We report the analysis of the role of one of the known DNA repair systems, nucleotide excision repair (NER), in somatic mutation. Epstein-Barrvirus-transformed B cells from patients with defects in NER (XP-B, XP-D, XP-V, and CS-A) were studied. Their heavy and light chain genes show a high frequency of point mutations in the variable (V), but not in the constant (C) regions. This suggests that these B cells can undergo somatic hypermutation despite significant defects in NER. Thus, it is doubtful that NER is an essential part of the mechanism of somatic hypermutation of Ig genes. As an aside, NER seems also not involved in Ig gene switch recombination.

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Related in: MedlinePlus

Sequence alignments of heavy and light chain cDNAs from patients with XP-B, XP-D, XP-V and CS-A. On the top a general map of  heavy and light chain genes is shown. The individual maps below show the approximate positions of nucleotide changes compared with germline V  genes. Dotted lines represent unsequenced regions. As a control, ∼300 nucleotides of the constant regions of XPD-4, XPD2-1, XPD2-2, XPV-1, XPV-2,  XPV-3, CSA-1, CSA-2, and CSA-3 were sequenced; no mutations were found. *These two clones have the same V and J, but different N and D sequences.
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Figure 1: Sequence alignments of heavy and light chain cDNAs from patients with XP-B, XP-D, XP-V and CS-A. On the top a general map of heavy and light chain genes is shown. The individual maps below show the approximate positions of nucleotide changes compared with germline V genes. Dotted lines represent unsequenced regions. As a control, ∼300 nucleotides of the constant regions of XPD-4, XPD2-1, XPD2-2, XPV-1, XPV-2, XPV-3, CSA-1, CSA-2, and CSA-3 were sequenced; no mutations were found. *These two clones have the same V and J, but different N and D sequences.

Mentions: Fig. 1 shows various Ig clones obtained from each of the four cell lines and the region sequenced. We sequenced the D–J regions in the case of heavy chain genes and the J regions in the case of the light chain genes to confirm that individual clones are not represented in duplicates. Clones XPD4 and XPD2-2, for example, use the same V and J genes, but have distinctly different N regions and D regions (data not shown).


B lymphocytes of xeroderma pigmentosum or Cockayne syndrome patients with inherited defects in nucleotide excision repair are fully capable of somatic hypermutation of immunoglobulin genes.

Kim N, Kage K, Matsuda F, Lefranc MP, Storb U - J. Exp. Med. (1997)

Sequence alignments of heavy and light chain cDNAs from patients with XP-B, XP-D, XP-V and CS-A. On the top a general map of  heavy and light chain genes is shown. The individual maps below show the approximate positions of nucleotide changes compared with germline V  genes. Dotted lines represent unsequenced regions. As a control, ∼300 nucleotides of the constant regions of XPD-4, XPD2-1, XPD2-2, XPV-1, XPV-2,  XPV-3, CSA-1, CSA-2, and CSA-3 were sequenced; no mutations were found. *These two clones have the same V and J, but different N and D sequences.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2198998&req=5

Figure 1: Sequence alignments of heavy and light chain cDNAs from patients with XP-B, XP-D, XP-V and CS-A. On the top a general map of heavy and light chain genes is shown. The individual maps below show the approximate positions of nucleotide changes compared with germline V genes. Dotted lines represent unsequenced regions. As a control, ∼300 nucleotides of the constant regions of XPD-4, XPD2-1, XPD2-2, XPV-1, XPV-2, XPV-3, CSA-1, CSA-2, and CSA-3 were sequenced; no mutations were found. *These two clones have the same V and J, but different N and D sequences.
Mentions: Fig. 1 shows various Ig clones obtained from each of the four cell lines and the region sequenced. We sequenced the D–J regions in the case of heavy chain genes and the J regions in the case of the light chain genes to confirm that individual clones are not represented in duplicates. Clones XPD4 and XPD2-2, for example, use the same V and J genes, but have distinctly different N regions and D regions (data not shown).

Bottom Line: This suggests that these B cells can undergo somatic hypermutation despite significant defects in NER.Thus, it is doubtful that NER is an essential part of the mechanism of somatic hypermutation of Ig genes.As an aside, NER seems also not involved in Ig gene switch recombination.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Chicago, Illinois 60637, USA.

ABSTRACT
Recent experiments have strongly suggested that the process of somatic mutation is linked to transcription initiation. It was postulated that a mutator factor loads onto the RNA polymerase and, during elongation, causes transcriptional arrest that activates DNA repair, thus occasionally causing errors in the DNA sequence. We report the analysis of the role of one of the known DNA repair systems, nucleotide excision repair (NER), in somatic mutation. Epstein-Barrvirus-transformed B cells from patients with defects in NER (XP-B, XP-D, XP-V, and CS-A) were studied. Their heavy and light chain genes show a high frequency of point mutations in the variable (V), but not in the constant (C) regions. This suggests that these B cells can undergo somatic hypermutation despite significant defects in NER. Thus, it is doubtful that NER is an essential part of the mechanism of somatic hypermutation of Ig genes. As an aside, NER seems also not involved in Ig gene switch recombination.

Show MeSH
Related in: MedlinePlus