The laboratory of Dr. Wolf-Dietrich Heyer is internationally recognized for its expertise in molecular genetics and protein biochemistry with significant contributions to establish new paradigms and elucidate the fundamental mechanisms of DNA repair, particularly homologous recombination (HR). The most significant contributions include: the discovery of Mus81 (Interthal & Heyer, 2000), the definition of its substrate range (Ehmsen & Heyer, 2008, 2009), and of its cleavage mechanism (Mukherjee et al. 2014); the identification of the direct regulation of DNA repair by the DNA damage checkpoints and nonsense-mediated decay (Bashkirov et al. 2000, Herzberg et al. 2006, Janke et al. 2016); the illumination of the roles of Rad54 and Rdh54 in D-loop formation (Wright & Heyer, 2014, Piazza et al. 2019, Tavares et al. 2019, Shah et al. 2020); the regulation of human RAD54 by NEK1 kinase in collaboration with the Löbrich Lab (Spies et al. 2016) and the functions of Sgs1-Top3-Rmi1, Mph1, and Srs2 in D-loop disruption (Fasching et al. 2015, Liu et al. 2017, Piazza et al. 2019); the first reported (concomitant with two other laboratories) purification of full-length human BRCA2 (Liu et al. 2010), its regulation by DSS1 (Le et al. 2020), and its role to inhibit Pol theta-mediated end-joining in collaboration with the Löbrich lab (Llorens-Agost et al. 2021); the demonstration of the roles DNA Polymerases delta and lambda in HR (Li et al. 2009; Sneeden et al. 2013, Meyer et al. 2015, Cerqueira et al. 2023); the discovery of the anti-anti-recombination mechanism involving Rad55-Rad57 (Liu et al. 2011); the description of a novel and mutagenic HR sub-pathway, multi-invasion recombination, which involves genomic repeats and results in secondary DNA double-stranded breaks and rearrangements (Wright & Heyer, 2014, Piazza et al. 2017, Reitz et al. 2023 Genes Dev).