title: ALKBH1 is dispensable for abasic site cleavage during base excision repair and class switch recombination.
abstract: Potential roles of the abasic site lyase activity associated with AlkB homolog 1 (ALKBH1) were assessed by studies focusing on the two cellular processes that create abasic sites as intermediates: base excision repair and class switch recombination. Alkbh1(-/-) pups (lacking exon 3) were born at a lower than expected frequency from heterozygous parents, suggesting a reduced survival rate and non-Mendelian inheritance, and they exhibited a gender bias in favor of males (70% males and 30% females). To study ALKBH1's potential involvement in DNA repair, fibroblasts were isolated from Alkbh1(-/-) mice, spontaneously immortalized and tested for resistance to DNA damaging agents. Alkbh1(-/-) and isogenic cells expressing hALKBH1 showed no difference in survival to the DNA damaging agents methyl-methionine sulfate or H2O2. This result indicates that ALKBH1 does not play a major role in the base excision repair pathway. To assess ALKBH1's role in class switch recombination, splenic B cells were isolated from Alkbh1(-/-) and Alkbh1(+/+) mice and subjected to switching from IgM to IgG1. No differences were found in IgG1 switching, suggesting that Alkbh1 is not involved in class switch recombination of the immunoglobulin heavy chain during B lymphocyte activation.
authors.affiliation: Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, United States of America. tmueller@msu.edu
authors.forename: Tina A
authors.initials: TA
authors.lastname: Müller
authors.forename: Kefei
authors.initials: K
authors.lastname: Yu
authors.forename: Robert P
authors.initials: RP
authors.lastname: Hausinger
authors.forename: Katheryn
authors.initials: K
authors.lastname: Meek
mesh_terms: D000071498:AlkB Homolog 1, Histone H2a Dioxygenase; D000818:Animals; D004247:DNA / Q000737:chemistry* / Q000235:genetics*; D004260:DNA Repair / Q000187:drug effects; D045643:DNA Repair Enzymes / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005091:Exons / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017578:Immunoglobulin Class Switching / Q000187:drug effects; D008297:Male; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D004247:DNA; D008741:Methyl Methanesulfonate; D006861:Hydrogen Peroxide; C499236:ALKBH1 protein, human; D000071498:AlkB Homolog 1, Histone H2a Dioxygenase; C529511:Alkbh1 protein, mouse; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D045643:DNA Repair Enzymes