phase ses: Gap phase 1 , DNA synthesis phase, Gap phase 2, during which ABT-751 the cell prepares itself for division, and mitosis phase, during which the chromosomes separate and the cell divides. The M phase includes prophase, metaphase, anaphase, and telophase. Centrosome, the nonmembranous organelles that occupy a tiny volume near the center of the cell, are usually proximal to the nucleus. In most vertebrate cells, the centrosome is classically depicted as having two orthogonally positioned cylindrical centrioles surrounded by a matrix of fibrous and globular proteins that constitute the pericentriolar material. The cell cycle involves an intricate process of DNA replication and cell division that concludes with the formation of two genetically equivalent daughter cells.
In this progression, the centrosome is duplicated only once to produce the bipolar spindle and ensure proper chromosome segregation. Centrosome maturation and separation are tightly regulated Axitinib during the cell cycle. Centrosome duplication consists of the five morphological steps during cell cycle progression. 1 In early G1 S phase, the mother and daughter centrioles separate slightly and lose their orthogonal orientation, 2 in S phase, synthesis of a daughter centriole occurs in the vicinity of each preexisting centriole, 3 in G2 phase, the procentrioles elongate to complete the duplication proc ess. The duplicated centrosome disjoins into two functionally separate centrosome, each containing a motherdaughter pair of centrioles, 4 in late G2 phase, the centrosome increases in size and separate to allow the formation of a bipolar spindle, 5 in M phase, the original mother and daughter centrioles detach from each other in an event termed centrosome disjunction.
Since centrosome duplicates only once during the normal cell cycle, duplication of centrosome must proceed in coordination with DNA synthesis to synchronize with cell division. Centrosome appears to be a critical organelle for G2 M checkpoint. Centrosome separation is initiated at the G2 phase and completed in the M phase. Several key proteins involved in controlling the G2 M checkpoint have been shown to physically associate with centrosome. Centrosome associated regulators of G2 M checkpoint An increasingly number of cancer related proteins have been shown to reside in or traffic in and out of centrosomes.
These regulators include: 1 A number of cell cycleregulated proteins, including cyclin B1, Cdks, Chks, Plks, aurora kinases, and Neks, 2 Oncogenes, such as Survivin, Ras, Rad6, and HER2 neu, 3 Tumor suppressors including p53, Rb, p21, XRCC2 3, APC, NM23 R1 H1, Gadd45 and BRCA l 2, and 4 Ubiquitination and degradation related proteins, including anaphase promoting complex cyclosome , BRCA1, Cdc20, and Cdh1, 5 DNA damage checkpoint proteins including ATM, ATR, p53, BRCA1, Chk1, and Chk2. More detailed information about these regulators is listed in Table 1. The roles of these centrosome associated regulators have been extensively investigated and some of the current understanding of their roles in G2 M checkpoint and in response to DNA damage is summarized in Fig 1. In this section, we will review the regulatory roles of the key centrosome related kinases and some cancer related genes involved in G2 M transition. Cdc2 and its