What is ANAPHASE LAG? What does ANAPHASE LAG mean? ANAPHASE LAG meaning & explanation

BROWSE The Internet EASY way with The Audiopedia owned Lightina Browser Android app. INSTALL NOW - https://ift.tt/2SipMz9 What is ANAPHASE LAG? What does ANAPHASE LAG mean? ANAPHASE LAG meaning - ANAPHASE LAG definition - ANAPHASE LAG explanation. Source: Wikipedia.org article, adapted under https://ift.tt/yjiNZw license. One of many ways to induce Aneuploidy, Anaphase Lag is a mechanism by which a sister chromatid is lost through the course of cell division due to improper spindle formation and subsequent segregation of chromatids. This event can occur during both meiosis and mitosis with unique repercussions. In either case, anaphase lag will cause one daughter cell to receive a complete set of chromosomes while the other lacks one paired set of chromosomes, creating a form of monosomy. The survival of this monosomic daughter cell will depend on which sister chromatid has been lost as well as the background genomic state of the cell. The passage of abnormal numbers of chromosomes will have unique consequences with regards to mosaicism and development as well as the progression and heterogeneity of cancers. There are two notable mechanisms that cause Anaphase Lag, each of which are characterized by merotelic attachments of kinetochores to the microtubules responsible for chromatid separation. Merotelic attachments occur when a single centromere kinetochore attaches to microtubules originating from both spindle poles of the dividing cell. The merotelic attachments can occur in two ways: centrosome spindle attachments from both poles on the same chromatid kinetochore or the formation of a third centrosome whose microtubule spindles attach to a chromatid kinetochore. Because the chromatid is being pulled in two opposing directions or away from the correct centriole, it cannot migrate to the mass of segregated chromatids at either pole. If the migration is significantly delayed the reformation of nuclei will begin to occur without a full complement of chromosomes. This nuclear envelope formation is also seen for the lone lagging sister chromatid, forming a micronucleus. The micronucleus has the capacity to persist in the daughter cell but with abnormal replication and maintenance machinery. This allows for the accumulation of mutations, increasing the potential for future miss-segregation events. In total these events cause problematic aneuploid cells with increased genomic instability. This has important implications in the development and persistence of cancers as well as debilitating developmental diseases. One of the hallmarks of cancer formation and persistence is genomic instability, referring to the increased frequency in sequence mutation, chromosome rearrangement, and aneuploidy. The instability allows a cancerous growth to increasingly diverge from normal cell growth and division, with the potential to gain new traits such as angiogenesis, immune system evasion, and loss of cell cycle checkpoint genes. Aneuploidy is a drastic divergence from the normal karyotype, as such the potential heterogeneity within these cells makes diagnosis and treatment increasingly difficult. The increasing importance of genomic instability on cancer progression has been emphasized in recent years. There are many ways to cause aneuploidy, however the genomic predispositions for these events are less well understood. In regards to the merotelic kinetochore attachments associated with anaphase lag, several genes have been implicated. Aurora B is a kinase active in late metaphase, and has been shown to function as a checkpoint for the proper attachments of centriole spindles to the chromatid kinetochores. When Aurora B was partially inhibited by a small molecule drug, Cimini et. al. observed lagging chromatids at increasing frequency. Similarly, mutations to the gene Stag2 have been associated with increased aneuploidy in cancers. Stag2 encodes a cohesin protein responsible for holding sister chromatids together pre-anaphase. Imaging of cells with Stag2 knock-outs showed increased frequency of lagging anaphase chromatids; subsequent gene correction in human glioblastoma cell lines reduced the occurrence of this genomic instability....