Reprint of “The clinical impact of deficiency in DNA non-homologousend-joining”

Woodbine, Lisa, Gennery, Andrew R and Jeggo, Penny A (2014) Reprint of “The clinical impact of deficiency in DNA non-homologousend-joining”. DNA Repair, 17. pp. 9-20. ISSN 1568-7864

PDF - Published Version
Download (1MB) | Preview


DNA 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.

Item Type: Article
Keywords: Mammalian cellsDouble strand break repairV(D)J recombination(Severe) combined immunodeficiency –(S)CIDHuman syndromesa
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science > QD Chemistry > QD0241 Organic chemistry > QD0415 Biochemistry
Depositing User: Gee Wheatley
Date Deposited: 04 Aug 2015 12:57
Last Modified: 24 Mar 2017 12:54

View download statistics for this item

📧 Request an update