Genome editing holds great promise for fundamental discovery, treatment of genetic diseases, and prophylactic treatment. Gene knockouts can be generated using a genome editing endonuclease (e.g., a zinc finger nuclease (ZFN), a transcription activator-like effector nuclease (TALEN), a CRISPR/Cas protein: guide RNA, and the like) to introduce a site-specific double strand break (DSB) within a gene of interest. Clones can be screened for those in which one or more alleles have been repaired in an error-prone fashion to disrupt the open reading frame. However, genome editing reagents can have differential activities, for example variable knockout efficiency stemming from the use of different CRISPR guide RNAs. Thus, there is a need for methods and compositions for increasing the frequency of disrupting mutations (e.g., indels) that can be produced when using targeted genome editing nucleases. UC Berkeley researchers have discovered a simple way to increase the frequency of the generation of indels gene editing reagents by adding non-homologous DNA to the genome targeting composition (e.g., zinc finger nuclease, TALEN nuclease fusion protein, CRISPR/Cas endonuclease). This approach greatly increases the frequency of knockout alleles, thereby enabling the easy generation of homozygous knockout cell lines and organisms, as well as improving the efficiency of knockout screens.