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Anti-TopBP1 Antibody, Alexa Fluor(R) 488 Conjugate from rabbit, ALEXA FLUOR(R) 488

ITEM#: 3042-AB3245IAF488

MFR#: AB3245-I-AF488

DNA topoisomerase 2-binding protein 1 (UniProt Q92547; also known as DNA topoisomerase II-beta-binding protein 1, DNA topoisomerase II-binding protein 1, TopBP1) is encoded by the TOPBP1 (also known as KIAA0259) gene (Gene ID 11073) in human. Timely

DNA topoisomerase 2-binding protein 1 (UniProt Q92547; also known as DNA topoisomerase II-beta-binding protein 1, DNA topoisomerase II-binding protein 1, TopBP1) is encoded by the TOPBP1 (also known as KIAA0259) gene (Gene ID 11073) in human. Timely DNA replication and accurate chromosome segregation is critical for maintaining genome integrity to avoid cancer and other genetic diseases. TopBP1 plays an important role in mediating DNA processing during mitosis to reduce transmission of DNA damage toG1 daughter cells. Unlike the translesion synthesis scaffold factor Rev1 or K164-ubiquitylated PCNA that serve to recruit translesion polymerases to stalled forks, TopBP1 forms foci upon mitotic entry, marking sites of and promoting unscheduled DNA synthesis at underreplicated regions independent of Rev1 and PCNA. Persistent TopBP1 foci transition into 53BP1 nuclear bodies (NBs) in G1 and precise temporal depletion of TopBP1 just before mitotic entry induces formation of 53BP1 NBs in the next cell cycle. Human TopBP1 contains eight BRCA1 C Terminus (BRCT) domains (a.a. 101-189, 195-284, 354-444, 548-633, 641-738, 900-991, 1259-1351, 1389-1486) and two nuclear localization signal (NLS) motifs (a.a. 852-858, 1517-1520). TopBP1 BRCT1/2-mediated interaction with phosphorylated Rad9 is essential for TopBP1-dependent ATR (ataxia telangiectasia and Rad3-related) activation, while TopBP1 BRCT6 interacts with the phosphorylated transcription factor, E2F1 to repress E2F1 activity in response to DNA damage. BRCT6 is also targeted for poly(ADP-ribosyl)ation by poly(ADP-ribose) polymerase 1 (PARP-1). The innate immune regulator STAT-5 is activated by human papillomavirus (HPV) proteins in HIV-infected cells, resulting in upregulated TopBP1 transcription and ATR pathway activation required for HPV genome amplification.