We’ve got lately described hSNMB as being a new gene associated with this cellular response to DNA harm . The hSNMB protein belongs on the SNM family. The frequent characteristics on the proteins on this group are two domains, a metallo lactamase domain and a CASP region, that are characteristic of members with the lactamase superfamily of proteins which interact with nucleic acids . The sequence similarity amongst the SNM members of the family is limited to these two areas that are conserved from yeast to mammals. ARTEMIS may be the very best investigated member from the SNM family with an established function in DNA overhang processing and opening of DNA hairpins generated during non homologous end joining and V J recombination . In some instances mutations in the ARTEMIS gene have been shown to be the underlying cause of severe mixed immunodeficiency in association with radiosensitivity . Based on its similarity on the S. cerevisiae SNM gene, we initially identified the human KIAA hSNM gene as a prospective human DNA crosslink repair gene with an unusually long UTR , a function which was later on shown to play a role in the regulation of hSNM translation .
Mouse embryonic stem cells during which mSNM is disrupted show a twofold lessen within their survival on exposure toMitomycin C , but to not other DNA crosslinking agents or ionizing radiation . Nonetheless, remedy with either IR or MMC does result in an increased quantity of nuclear hSNM foci , suggesting that hSNM responds in some strategy to the two DNA double strand breaks and interstrand cross backlinks . Also, mammalian SNM has become MK 801 selleckchem implicated in an early mitotic strain checkpoint, in tumor suppression, and immunity . In contrast to the DNA harm response roles identified for Artemis and hSNM, a few groups have not long ago advised that hSNMB functions mostly in telomere protection. Freibaum and Counter observed transiently expressed EGFPhSNMB colocalized and Co immunoprecipitated with TRF . An alternative group recognized this interaction by using a combination of Co immunoprecipitation and mass spectrometry . Lastly, using a fragment of TRF like a bait, Lenain et al.
located hSNMB as an interactor within a yeast two hybrid display . These research showed that transiently expressed hSNMB fused with GFP or perhaps a myc tag localizes to telomeres. Following hSNMB Tacrolimus knockdown, the phenotype of TRF inhibited cellswas exacerbated in terms of growth defects, telomere deprotection and greater fusions . Activation of a DNAdamage signal at telomeres was observed as a consequence of hSNMB knockdown . Altogether these current findings strongly recommend that hSNMB cooperates with TRF to guard telomeres from getting acknowledged as damaged DNA. Our own prior scientific studies of hSNMB have recommended a far more standard position for your protein from the cellular response to the two DNA double strand breaks or interstrand crosslinks .