description
Mitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cyclin-dependent kinases (CDKs) are key regulatory enzymes, each consisting of a catalytic CDK subunit and an activating cyclin subunit. CDKs regulate the cell's progression through the phases of the cell cycle by modulating the activity of key substrates. Downstream targets of CDKs include transcription factor E2F and its regulator Rb. Precise activation and inactivation of CDKs at specific points in the cell cycle are required for orderly cell division. Cyclin-CDK inhibitors (CKIs), such as p16Ink4a, p15Ink4b, p27Kip1, and p21Cip1, are involved in the negative regulation of CDK activities, thus providing a pathway through which the cell cycle is negatively regulated. Eukaryotic cells respond to DNA damage by activating signaling pathways that promote cell cycle arrest and DNA repair. In response to DNA damage, the checkpoint kinase ATM phosphorylates and activates Chk2, which in turn directly phosphorylates and activates p53 tumor suppressor protein. p53 and its transcriptional targets play an important role in both G1 and G2 checkpoints. ATR-Chk1-mediated protein degradation of Cdc25A protein phosphatase is also a mechanism conferring intra-S-phase checkpoint activation

external resources
NCBI:83054
KEGG:hsa04110
PUBMED:7973727
PUBMED:17568790
PUBMED:9832503
PUBMED:16936746
PUBMED:9029154
PUBMED:12573239
PUBMED:19020303
PUBMED:9618481
PUBMED:12809600
PUBMED:8242749
PUBMED:10385618
PUBMED:17426725
PUBMED:17018296
PUBMED:16212951
PUBMED:12925736
PUBMED:11099028
PUBMED:15568976
PUBMED:15838516
PUBMED:15838523
PUBMED:15876871
PUBMED:7908906
PUBMED:9889196

genes
ABL1 , ATM , ATR , CCND1 , BUB1 , BUB1B , CCNA2 , CCNB1 , CCND2 , CCND3 , CCNE1 , CCNH , CDK1 , CDC6 , CDC20 , CDC25A , CDC25B , CDC25C , CDC27 , CDK2 , CDK4 , CDK6 , CDK7 , CDKN1A , CDKN1B , CDKN1C , CDKN2A , CDKN2B , CDKN2C , CDKN2D , CHEK1 , CREBBP , GADD45A , E2F1 , E2F2 , E2F3 , E2F4 , E2F5 , EP300 , SFN , GSK3B , HDAC1 , HDAC2 , MAD2L1 , SMAD2 , SMAD3 , SMAD4 , MCM2 , MCM3 , MCM4 , MCM5 , MCM6 , MCM7 , MDM2 , MYC , GADD45B , ORC1 , ORC2 , ORC4 , ORC5 , PCNA , PLK1 , PRKDC , RAD21 , RB1 , RBL1 , RBL2 , SKP1 , SKP2 , TFDP1 , TFDP2 , TGFB1 , TGFB2 , TGFB3 , TP53 , TTK , WEE1 , YWHAB , YWHAE , YWHAG , YWHAH , YWHAZ , ZBTB17 , SMC1A , CDC7 , CDC45 , MAD1L1 , CUL1 , CDC14B , CDC14A , CDC23 , CDC16 , CCNA1 , PKMYT1 , SMC3 , CCNB2 , CCNE2 , BUB3 , PTTG1 , ESPL1 , RBX1 , STAG1 , ANAPC10 , MAD2L2 , STAG2 , PTTG2 , GADD45G , DBF4 , YWHAQ , CHEK2 , ORC6 , ORC3 , ANAPC13 , SMC1B , ANAPC2 , ANAPC4 , FZR1 , ANAPC5 , ANAPC7 , ANAPC11 , ANAPC1 , CCNB3 , CDC26 , WEE2 ,