Class switch recombination (CSR) is a region-specific, transcriptionally regulated, nonhomologous recombinational process that is initiated by activation-induced cytidine deaminase (AID). The initial lesions in the switch (S) regions are subsequently processed and resolved, leading to recombination of the two targeted S regions. The mechanisms by which repair and ligation of the broken DNA ends occurs is still elusive. Recently, a small number of patients lacking DNA ligase IV, a critical component of the nonhomologous end joining (NHEJ) machinery, have been identified. We show that these patients display a considerably increased donor/acceptor homology at Sμ–Sα junctions compared with healthy controls. In contrast, Sμ–Sγ junctions show an increased frequency of insertions but no increase in junctional homology. These altered patterns of junctional resolution may be related to differences in the homology between the Sμ and the downstream isotype S regions, and could reflect different modes of switch junction resolution when NHEJ is impaired. These findings link DNA ligase IV, and thus NHEJ, to CSR.
Skip Nav Destination
Article navigation
17 January 2005
Brief Definitive Report|
January 18 2005
Impact of DNA ligase IV on nonhomologous end joining pathways during class switch recombination in human cells
Qiang Pan-Hammarström,
Qiang Pan-Hammarström
1Clinical Immunology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, SE-14186 Stockholm, Sweden
Search for other works by this author on:
Anne-Marie Jones,
Anne-Marie Jones
2Department of Medicine, University College London, London W1T 4NJ, England, UK
Search for other works by this author on:
Aleksi Lähdesmäki,
Aleksi Lähdesmäki
1Clinical Immunology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, SE-14186 Stockholm, Sweden
Search for other works by this author on:
Wei Zhou,
Wei Zhou
1Clinical Immunology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, SE-14186 Stockholm, Sweden
Search for other works by this author on:
Richard A. Gatti,
Richard A. Gatti
3Department of Pathology, University of California Los Angeles School of Medicine, CA 90095
Search for other works by this author on:
Lennart Hammarström,
Lennart Hammarström
1Clinical Immunology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, SE-14186 Stockholm, Sweden
Search for other works by this author on:
Andrew R. Gennery,
Andrew R. Gennery
4Department of Pediatric Immunology, Newcastle General Hospital, Newcastle NE4 6BE, England, UK
Search for other works by this author on:
Michael R. Ehrenstein
Michael R. Ehrenstein
2Department of Medicine, University College London, London W1T 4NJ, England, UK
Search for other works by this author on:
Qiang Pan-Hammarström
1Clinical Immunology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, SE-14186 Stockholm, Sweden
Anne-Marie Jones
2Department of Medicine, University College London, London W1T 4NJ, England, UK
Aleksi Lähdesmäki
1Clinical Immunology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, SE-14186 Stockholm, Sweden
Wei Zhou
1Clinical Immunology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, SE-14186 Stockholm, Sweden
Richard A. Gatti
3Department of Pathology, University of California Los Angeles School of Medicine, CA 90095
Lennart Hammarström
1Clinical Immunology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, SE-14186 Stockholm, Sweden
Andrew R. Gennery
4Department of Pediatric Immunology, Newcastle General Hospital, Newcastle NE4 6BE, England, UK
Michael R. Ehrenstein
2Department of Medicine, University College London, London W1T 4NJ, England, UK
CORRESPONDENCE Michael Ehrenstein: [email protected] or Qiang Pan-Hammarström: [email protected]
Received:
April 19 2004
Accepted:
December 07 2004
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2005
J Exp Med (2005) 201 (2): 189–194.
Article history
Received:
April 19 2004
Accepted:
December 07 2004
Citation
Qiang Pan-Hammarström, Anne-Marie Jones, Aleksi Lähdesmäki, Wei Zhou, Richard A. Gatti, Lennart Hammarström, Andrew R. Gennery, Michael R. Ehrenstein; Impact of DNA ligase IV on nonhomologous end joining pathways during class switch recombination in human cells . J Exp Med 17 January 2005; 201 (2): 189–194. doi: https://doi.org/10.1084/jem.20040772
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionEmail alerts
Advertisement