Independent function of Slx4 in budding yeast. SLX4-Rtt107 competes with Rad9 for Dpb11 and phosphorylated H2A binding, which final results in down-regulation of Rad53 activity and associated DNA damage checkpoint.et al., 2013). Since the SLX4-SLX1 complicated has HJ resolvase activity, it was initially proposed that SLX1 nuclease activity plays a part in homologous recombination throughout the ICL repair (Munoz et al., 2009; Svendsen and Harper, 2010). Having said that, expression of nuclease dead SLX1 fused to archaeal resolving enzyme Hje (Hje-SLX1mut) in SLX1 deficient MEF fails to complement MMC sensitivity, but restores Holliday junction resolvase activity. These results imply that SLX1’s function in ICL repair includes cleavage of DNA intermediates instead of Holliday junctions. The target DNA intermediates of SLX1 through ICL repair Rimsulfuron Data Sheet remain elusive. Roles of MUS81-EME1 in ICL repair MUS81 deficient mice are fertile, born at normal Mendelian frequencies with no overt abnormalities (Dendouga et al., 2005) but cells from MUS81 deficient mice are sensitive to DNA crosslinking agents (Hanada et al., 2006; McPherson et al., 2004). The SAP domain of human SLX4 is responsible for SLX4MUS81 interaction, and expression in the SAP domain deletion SLX4 mutant in human SLX4 null cells partially rescue the MMC sensitivity in the FANCP cells, suggesting that the function of MUS81 in ICL repair is determined by SLX4-MUS81 interaction. These findings are additional supported by the results showing that depletion of MUS81 in FANCP cells outcomes within the same MMC sensitivity because the FANCP cells. Interestingly, expression of mouse SLX4 mutants (L1348A and L1351A L1352A) that can’t interact with MUS81 had been able to rescue the MMC sensitivity of SLX4-/- MEF to the very same level as wildtype SLX4 (Castor et al., 2013). These findings recommend that the L-Norvaline Autophagy interaction of SLX4-MUS81 just isn’t essential for the function of MUS81 in ICLrepair at least in mice, but non-SLX4-associated MUS81 might play a role in ICL repair. The SAP domain might have more function for regulating SLX4 activities in ICL repair besides the interaction with MUS81 (Castor et al., 2013). Understanding the discrepancy of MUS81’s function in ICL repair in human and mice will be fascinating to study.ROLES OF SLX4 AS A HOLLIDAY JUNCTION RESOLVASEHJ is usually a crusade kind of DNA intermediate arising at the very last step of homologous recombination through DNA double strand break repair and restoration of stalled replication forks (Liu and West, 2004). The HJ processing is necessary for the completion of DNA repair pathways and for chromosome segregation during mitosis (Li and Heyer, 2008; Sung and Klein, 2006). In eukaryotes, HJ is processed either by dissolution or by resolution. The HJ dissolution is mediated by BLM-TOP3RMI1-RMI2 complicated (Wu and Hickson, 2006). Even though molecular mechanism of HJ dissolution in human is fairly properly understood, the resolution isn’t. In E. coli, the HJs are resolved by RuvC which introduces symmetrical nicks to the HJ to resolve it and simply religates the nicks to finish the resolution. On the other hand, SLX4-SLX1 complex introduces nicks but these nicks are not symmetric and cannot be basically ligated, and these findings raise a query if MUS81 bound to SLX4 with each other with SLX1 may possibly cooperatively resolve the HJs. In eukaryotes, in vitro biochemical assays showed that 3 nucleases, GEN1, MUS81-EME1 and SLX4-SLX1, are capable of resolving HJs (Svendsen and Harper, 2010). Lately, physiological.