Summary of the 2021 Mammalian DNA Repair GRC and GRS This 5-day GRC + 1.5-day GRS conference is focused on the research of genomic instability and its implications in human diseases and therapies. The human genome is constantly threatened by DNA damage caused by environmental insults and various cellular processes occurring in DNA. Common environmental mutagens include radiation, aldehydes, and dioxins. Cellular processes such as DNA replication, transcription and mitosis can also give rise to DNA damage when dysregulated. In normal cells, a multitude of DNA repair and DNA damage response mechanisms successfully operate to maintain genomic stability. However, defects in these mechanisms can result in diseases ranging from rare developmental and premature aging syndromes to common cancers. This Mammalian DNA Repair Gordon Research Conference (GRC) and associated Gordon Research Seminar (GRS) will bring together diverse researchers studying the mechanisms that protect the genome against DNA damage, and the implications of these mechanisms in human diseases such as cancer. In addition, the conference will promote discussions on how to target defects of the DNA damage response in cancer therapy, and how to gain a better understanding of tumor evolution and therapeutic responses through genomic approaches. The objectives are: 1) To expose researchers at all levels (faculty, researchers from industry, postdoctoral fellows, and graduate students) to new frontiers of this rapidly progressing research field. 2) To provide opportunities for young scientists to network and practice presenting their research. 3) To generate an atmosphere of inclusion and rigor that encourages the exchange of scientific ideas that may foster collaborations or spur new innovation.4) To provide formal and informal career development opportunities. We will achieve these objectives by assembling diverse speakers and poster presenters. 40% of the invited speakers in the GRC are women and we expect approximately 45% of the GRS speakers be female trainees. This GRC/GRS is notable compared to meetings on similar topics for the amount of unpublished research that is presented, as well as the extensive informal discussion time during sessions, meals, and free time.