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One of the hallmark features of eukaryotic cells is the presence of a nucleus that separates chromosomes from cytoplasm by the NE The NE mostly consists of lipids integral membrane proteins and protein complexes such as nuclear pore complexes NPCs Outer nuclear membrane ONM is continuous with ER and connects with the inner nuclear membrane INM at NPCs NEs essentially are at the center of genome integrity and mitosis both of which are causative factors in a variety of cell disorders including cancer and aging Nuclei are generally spherical in order to contain everything in minimum volume andany changes in nuclear rigidity would alter the shape of the nucleus Altered nuclear morphology can be attributed to change in intra-nuclear chromosome organization and gene expression improper SPB positioning and thereby improper chromosome segregation Altered rigidity from the loss of circularity also facilitates formation of metastases Figure 1 shows an abnormal shaped multi-lobed nucleus of metastatic adrenocarcinomaMDA-MB-231 cells1 In higher eukaryotic cells nuclear laminas lamins are found with the INM which is generally attached by farnesylation Nuclear lamins along with lamin associated proteins are attached with transcriptionally inactive chromosomes and contribute to intranuclear chromosome arrangements Mutation and defects in these lamins cause a variety of diseases and pathological disorders collectively known as laminopathies These are directly linked to abnormal shapes of the nucleus and NE abnormal fat tissue formation and premature aging2 Figure 2 shows the shape of the nuclei of a 9 year old a 96 year old and a HutchinsonGilford progeria syndrome HGPS patient that clearly demonstrate the correlation ship among NE abnormality and aging related disorders3One of the NE protein Sad1 UNC 84 Domain Containing Sun proteins present in the inner nuclear membrane INM is critical for maintaining the proper shape of the nucleus Sun proteins bind with KASH proteins at the outer nuclear envelope which associate with cytoplasmic tubulins together called LINC complex4 Sun proteins also bind with lamins inside the nucleus thereby
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