motifs/domains
| an additional cryptic BRCT domain (BRCT0) at the extreme N terminus  |
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an auto-ADP-ribosylation site |
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several chromatin modification domains |
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eight other BRCT domains, and BRCT domains 4–5 interacted with TP53BP1 and recruitment of TOPBP1 to sites of DNA DSBs in G1 was dependent on TP53BP1 |
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a phosphorylated SQ/TQ site within the ATR activation domain that enhance its ability to activate ATR/ATRIP complex |
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two C-terminal nuclear localization signals, a BRCA1 C-terminal motifs, AAs 1259 to 1420 in the TOPBP1 C-terminal region (TBPCtR) are involved in localization of TOPBP1 to the mitotic centrosomes |
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eight BRCT [BRCA1 (breast-cancer susceptibility gene 1) C-terminus] domains |
SUBCELLULAR LOCALIZATION
| intracellular
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| intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
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| intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
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| intracellular,nucleus
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| text
| colocalizes with TP53BP1 at sites of DNA double-strand breaks (DSBs), but only in the G1-phase of the cell cycle |
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in prometaphase, metaphase, and anaphase, localizes to the mitotic centrosomes, which function as spindle-poles for the bipolar separation of sister chromatids, and localization to the mitotic centrosomes is necessary for proper mitotic progression |
| basic FUNCTION
| required for DNA replication |
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playing a role in the rescue of stalled replication forks and checkpoint control |
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essential activator of the ATR kinase |
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recruiting the SWI/SNF chromatin remodeling complex to E2F1-responsive promoters |
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down-regulating E2F1 activity |
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inhibiting E2F1-dependent apoptosis during G1/S transition and after DNA damage |
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required for G(1) to S progression |
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activating ATR which is a crucial step in the initiation of ATR-dependent signaling processes |
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implicated in DNA damage response |
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could repress the expression of ABL1 at both mRNA and protein levels |
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involved in initiating DNA replication, and DNA damage checkpoint signalling and repair |
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involved in the formation of the initiation complex of replication in cells and is required for the recruitment of CDC45 to origins of DNA replication |
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plays a critical role in the control of DNA replication checkpoint |
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with BRIP1, are required for ATR-dependent phosphorylation events in response to replication stress |
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has important roles in both DNA replication and checkpoint regulation |
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essential for normal G(1)/S transition, but a pathological level of TOPBP1 in cancer may perturb TP53 function and contribute to an aggressive tumor behavior |
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crucial role in actively repressing TP53 |
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collaborate in the Cdk2-mediated loading of CDC45 onto replication origins |
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plays a critical role in the control of DNA replication checkpoint |
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TOPBP1 and BRIP1 are required for ATR-dependent phosphorylation events in response to replication stress |
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checkpoint protein that colocalizes with ATR at sites of DNA replication stress |
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scaffold protein that coordinates activation of the DNA-damage-checkpoint response by coupling binding of the 9-1-1 checkpoint clamp at sites of ssDNA |
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may mediate the checkpoint function of TP53BP1 in G1 |
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emergence of TOPBP1 as a key regulator in the DNA replication checkpoint pathway is underscored by its multiple roles contributing to the activation of ATR |
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its role as an integrator of diverse signals that control the replication stress response critically depends on its nine BRCT domains that dictate diverse molecular interactions |
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plays important roles in chromosome replication, DNA damage response, and other cellular regulatory functions, and is essential for cell proliferation during early embryogenesis |
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triggers cellular senescence in human primary cells |
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plays important roles in DNA damage response, DNA replication, and other cellular regulatory functions during the interphase |
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required for the initiation of DNA replication and for DNA repair and damage signalling |
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plays multiple roles in the regulation of DNA damage checkpoint signaling |
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WDR18 is a bona fide checkpoint protein and works together with TOPBP1 to promote DNA damage checkpoint signaling |
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NBN and TOPBP1 have the potential to activate ATR independently, although both are required for functional activation of ATR |
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TICRR like TOPBP1, is a dual replication/checkpoint protein that directly participates in ATR-mediated checkpoint signaling |
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controls BLM protein level to maintain genome stability |
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role in HR, with potential clinical implications for cancer treatment |
