Small molecules enhance knock-in efficiency. (A) Small molecules related to the NHEJ or HDR repair pathway. Inhibitors are labeled in red, activators are labeled in blue. NU7026 inhibits DNA-PK, and SCR7, E1B55K, and E4orf6 inhibit DNA ligase IV. MLN4924, NSC15520, RS-1, Trichostatin A, or Resveratrol enhance CtIP, RPA, RAD51, or ATM, respectively. ATM protein also induces activation of RPA, BRCA2, and RAD51. The i53 is an inhibitor of 53BP1. The i53 activates DNA end resection and recruitment, of BRCA1 to DSBs. (B) HDR activity is increased at S/G2 phase. NHEJ activity is labeled in blue, HDR activity is labeled in red. Small molecules are used to arrest the cell cycle at specific phase, to improve HDR efficiency. L755505, Resveratrol, Mimosine, Aphidicolin, Thymidine and Hydroxyurea block cells at the G1 to S phase before DNA replication, and Nocodazole arrests cell cycle at G2/M phase. Lovastatin also inhibits at early G1, and partially at G2/M phase.