TOPBP1 report

I. Expression across cell types

II. Expression across tissues

III. Associated gene sets

GO_0006325Biological processchromatin organization
GO_0006281Biological processDNA repair
GO_0010212Biological processresponse to ionizing radiation
GO_0006974Biological processDNA damage response
GO_0097681Biological processdouble-strand break repair via alternative nonhomologous end joining
GO_0097680Biological processdouble-strand break repair via classical nonhomologous end joining
GO_0000724Biological processdouble-strand break repair via homologous recombination
GO_0007095Biological processmitotic G2 DNA damage checkpoint signaling
GO_0141112Biological processbroken chromosome clustering
GO_0006259Biological processDNA metabolic process
GO_0051276Biological processchromosome organization
GO_0006270Biological processDNA replication initiation
GO_0035825Biological processhomologous recombination
GO_1990166Biological processprotein localization to site of double-strand break
GO_0033314Biological processmitotic DNA replication checkpoint signaling
GO_0000076Biological processDNA replication checkpoint signaling
GO_0000077Biological processDNA damage checkpoint signaling
GO_0005886Cellular componentplasma membrane
GO_0000922Cellular componentspindle pole
GO_0005813Cellular componentcentrosome
GO_0005654Cellular componentnucleoplasm
GO_0090734Cellular componentsite of DNA damage
GO_0015629Cellular componentactin cytoskeleton
GO_0016604Cellular componentnuclear body
GO_0016605Cellular componentPML body
GO_0005737Cellular componentcytoplasm
GO_0070532Cellular componentBRCA1-B complex
GO_0005694Cellular componentchromosome
GO_0000794Cellular componentcondensed nuclear chromosome
GO_0001673Cellular componentmale germ cell nucleus
GO_0035861Cellular componentsite of double-strand break
GO_0005634Cellular componentnucleus
GO_0003677Molecular functionDNA binding
GO_0140463Molecular functionchromatin-protein adaptor activity
GO_0042802Molecular functionidentical protein binding
GO_0043539Molecular functionprotein serine/threonine kinase activator activity
GO_0140031Molecular functionphosphorylation-dependent protein binding
GO_0005515Molecular functionprotein binding

IV. Literature review

[source]
Gene nameTOPBP1
Protein nameDNA topoisomerase II binding protein 1
TOPBP1 protein
DNA topoisomerase 2-binding protein 1 (DNA topoisomerase II-beta-binding protein 1) (TopBP1) (DNA topoisomerase II-binding protein 1)
Topoisomerase (DNA) II binding protein 1
SynonymsKIAA0259
DescriptionFUNCTION: Scaffold protein that acts as a key protein-protein adapter in DNA replication and DNA repair . Composed of multiple BRCT domains, which specifically recognize and bind phosphorylated proteins, bringing proteins together into functional combinations . Required for DNA replication initiation but not for the formation of pre-replicative complexes or the elongation stages (By similarity). Necessary for the loading of replication factors onto chromatin, including GMNC, CDC45, DNA polymerases and components of the GINS complex (By similarity). Plays a central role in DNA repair by bridging proteins and promoting recruitment of proteins to DNA damage sites . Involved in double-strand break (DSB) repair via homologous recombination in S-phase by promoting the exchange between the DNA replication factor A (RPA) complex and RAD51 . Mechanistically, TOPBP1 is recruited to DNA damage sites in S-phase via interaction with phosphorylated HTATSF1, and promotes the loading of RAD51, thereby facilitating RAD51 nucleofilaments formation and RPA displacement, followed by homologous recombination . Involved in microhomology-mediated end-joining (MMEJ) DNA repair by promoting recruitment of polymerase theta (POLQ) to DNA damage sites during mitosis . MMEJ is an alternative non-homologous end-joining (NHEJ) machinery that takes place during mitosis to repair DSBs in DNA that originate in S-phase . Recognizes and binds POLQ phosphorylated by PLK1, enabling its recruitment to DSBs for subsequent repair . Involved in G1 DNA damage checkpoint by acting as a molecular adapter that couples TP53BP1 and the 9-1-1 complex . In response to DNA damage, triggers the recruitment of checkpoint signaling proteins on chromatin, which activate the CHEK1 signaling pathway and block S-phase progression . Acts as an activator of the kinase activity of ATR . Also required for chromosomal stability when DSBs occur during mitosis by forming filamentous assemblies that bridge MDC1 and tether broken chromosomes during mitosis . Together with CIP2A, plays an essential role in the response to genome instability generated by the presence of acentric chromosome fragments derived from shattered chromosomes within micronuclei . Micronuclei, which are frequently found in cancer cells, consist of chromatin surrounded by their own nuclear membrane: following breakdown of the micronuclear envelope, a process associated with chromothripsis, the CIP2A-TOPBP1 complex tethers chromosome fragments during mitosis to ensure clustered segregation of the fragments to a single daughter cell nucleus, facilitating re-ligation with limited chromosome scattering and loss . Recruits the SWI/SNF chromatin remodeling complex to E2F1-responsive promoters, thereby down-regulating E2F1 activity and inhibiting E2F1-dependent apoptosis during G1/S transition and after DNA damage . .

AccessionsA0A2R8YD63
ENST00000642236.1
ENST00000572787.1
A0AV47
Q05BV8
I3L1F2
ENST00000260810.10
Q92547
A7E2X7