Woodbine_et_al-The_clinical_impact_of_deficiency_in_DNA_non-homologous_end-joining.pdf (1.54 MB)
Reprint of “The clinical impact of deficiency in DNA non-homologousend-joining”
journal contribution
posted on 2023-06-08, 22:02 authored by Lisa Woodbine, Andrew R Gennery, Penny JeggoDNA non-homologous end-joining (NHEJ) is the major DNA double strand break (DSB) repair pathway inmammalian cells. Defects in NHEJ proteins confer marked radiosensitivity in cell lines and mice models,since radiation potently induces DSBs. The process of V(D)J recombination functions during the devel-opment of the immune response, and involves the introduction and rejoining of programmed DSBs togenerate an array of diverse T and B cells. NHEJ rejoins these programmed DSBs. Consequently, NHEJdeficiency confers (severe) combined immunodeficiency – (S)CID – due to a failure to carry out V(D)Jrecombination efficiently. NHEJ also functions in class switch recombination, another step enhancing Tand B cell diversity. Prompted by these findings, a search for radiosensitivity amongst (S)CID patientsrevealed a radiosensitive sub-class, defined as RS-SCID. Mutations in NHEJ genes, defining human syn-dromes deficient in DNA ligase IV (LIG4 Syndrome), XLF-Cernunnos, Artemis or DNA-PKcs, have beenidentified in such patients. Mutations in XRCC4 or Ku70,80 in patients have not been identified. RS-SCIDpatients frequently display additional characteristics including microcephaly, dysmorphic facial featuresand growth delay. Here, we overview the clinical spectrum of RS-SCID patients and discuss our currentunderstanding of the underlying biology.
History
Publication status
- Published
File Version
- Published version
Journal
DNA RepairISSN
1568-7864Publisher
ElsevierExternal DOI
Volume
17Page range
9-20Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2015-08-04First Open Access (FOA) Date
2015-08-04First Compliant Deposit (FCD) Date
2015-08-04Usage metrics
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