Defective DNA repair and increased genomic instability in Artemis-deficient XXXX cells.

@entity1 @entity13563 @entity2085 @entity19 @entity465 @entity942
In developing lymphocytes, the recombination activating gene endonuclease cleaves DNA between V, D, or J coding and @entity13563 ( @entity13563 ) sequences to form hairpin coding and blunt @entity13563 ends, which are fused to form coding and @entity13563 joins. Nonhomologous end joining (NHEJ) factors repair DNA double strand breaks including those induced during VDJ recombination. @entity1 radiosensitive severe @entity465 results from lack of Artemis function, an NHEJ factor with in vitro endonuclease/exonuclease activities. We inactivated Artemis in @entity19 @entity2085 ( @entity2085 ) cells by targeted mutation. @entity942 results in impaired VDJ coding, but not @entity13563 , end joining. In addition, Artemis-deficient @entity2085 cells are sensitive to a radiomimetic drug, but less sensitive to ionizing radiation. VDJ coding joins from Artemis-deficient @entity2085 cells, which surprisingly are distinct from the highly deleted joins consistently obtained from DNA-dependent protein kinase catalytic subunit-deficient @entity2085 cells, frequently lack deletions and often display large junctional palindromes, consistent with a hairpin coding end opening defect. Strikingly, Artemis-deficient @entity2085 cells have increased chromosomal instability including telomeric fusions. Thus, Artemis appears to be required for a subset of NHEJ reactions that require end processing. Moreover, Artemis functions as a genomic caretaker, most notably in prevention of translocations and telomeric fusions. As @entity942 is compatible with @entity1 life, Artemis may also suppress genomic instability in @entity1 .
