title: DNA polymerase beta is critical for genomic stability of sperm cells.
abstract: Maintaining genome integrity in germ cells is important, given that the germ cells produce the next generation of offspring. Base excision repair is a DNA repair pathway that is responsible for the repair of most endogenous DNA damage. A key enzyme that functions in this repair pathway is DNA polymerase beta (Pol β). We previously used conditional gene targeting to engineer mice with sperm deleted of the Pol B gene, which encodes Pol β. We characterized mutagenesis in the sperm of these mice and compared it to wild-type and mice heterozygous for the Pol B gene. We found that sperm obtained that were heterozygously or homozygously deleted of the Pol B gene exhibited increased mutation frequencies compared to wild-type sperm. We identified an increase in transition mutations in both heterozygously and homozygously deleted sperm, and the types of mutations induced suggest that a polymerase other than Pol β functions in its absence. Interestingly, most of the transversions we observed were induced only in heterozygous, compared with wild-type sperm. Our results suggest that haploinsufficiency of Pol β leads to increased frequencies and varieties of mutations. Our study also shows that Pol β is critical for genome stability in the germline.
authors.affiliation: Department of Therapeutic Radiology, The Yale Comprehensive Cancer Center, 333 Cedar Street, New Haven, CT 06520, USA.
authors.forename: Dawit
authors.initials: D
authors.lastname: Kidane
authors.forename: Shibani
authors.initials: S
authors.lastname: Dalal
authors.forename: Agnes
authors.initials: A
authors.lastname: Keh
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Liu
authors.forename: Daniel
authors.initials: D
authors.lastname: Zelterman
authors.forename: Joann B
authors.initials: JB
authors.lastname: Sweasy
mesh_terms: D000818:Animals; D001483:Base Sequence; D004249:DNA Damage; D019951:DNA Polymerase beta / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D004789:Enzyme Activation / Q000502:physiology; D042822:Genomic Instability; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009154:Mutation; D013094:Spermatozoa / Q000378:metabolism*
chemical_list: D019951:DNA Polymerase beta