Protein: DNA topoisomerase 2-binding protein 1 (DNA topoisomerase II-beta-binding protein 1) (TopBP1) (DNA topoisomerase II-binding protein 1) (Q92547)
Organism: Homo sapiens (Human)
Function: Required for DNA replication. Plays a role in the rescue of stalled replication forks and checkpoint control. Binds double-stranded DNA breaks and nicks as well as single-stranded DNA. Recruits the SWI/SNF chromatin remodeling complex to E2F1-responsive promoters. Down-regulates E2F1 activity and inhibits E2F1-dependent apoptosis during G1/S transition and after DNA damage. Induces a large increase in the kinase activity of ATR.
Subcellular location: Nucleus {ECO:0000269|PubMed:11395493, ECO:0000269|PubMed:12697828, ECO:0000269|PubMed:12773567}. Chromosome {ECO:0000269|PubMed:10498869, ECO:0000269|PubMed:11395493, ECO:0000269|PubMed:11714696, ECO:0000269|PubMed:15138768, ECO:0000269|PubMed:21482717, ECO:0000269|PubMed:21659603, ECO:0000269|PubMed:21777809, ECO:0000269|PubMed:26811421, ECO:0000269|PubMed:30898438, ECO:0000269|PubMed:35121901, ECO:0000269|PubMed:35597237, ECO:0000269|PubMed:35842428, ECO:0000269|PubMed:37316668, ECO:0000269|PubMed:37674080}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:15138768}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269|PubMed:15138768}. Note=Localizes to sites of DNA damage, such as double-stranded breaks (DSBs) (PubMed:10498869, PubMed:21482717, PubMed:21659603, PubMed:21777809, PubMed:30898438, PubMed:35842428, PubMed:37674080). Recruited to DNA double-strand break (DSBs) during S-phase following interaction with phosphorylated HTATSF1 (PubMed:35597237). Recruited to DSBs during mitosis following interaction with phosphorylated MDC1 (PubMed:30898438). Has a uniform nuclear distribution during G phase (PubMed:11395493). Colocalizes with BRCA1 at stalled replication forks during S phase (PubMed:11395493). In mitotic cells it colocalizes with BRCA1 at spindle poles and centrosomes during metaphase and anaphase (PubMed:11395493). Detected in discrete foci together with PML and numerous DNA repair enzymes after DNA damage by alkylating agents, UV or gamma irradiation (PubMed:12773567). Detected on unpaired autosomes in meiotic prophase cells (By similarity). Detected on X and Y chromosomes during later stages of prophase (By similarity). Colocalizes with ATR and H2AX at unsynapsed chromosome cores during prophase (By similarity). Localizes to broken chromosomes within micronuclei during interphase and following chromothripsis (PubMed:37165191, PubMed:37316668). Localization to broken chromosomes is mainly independent of MDC1 (PubMed:35121901, PubMed:37165191). {ECO:0000250|UniProtKB:Q6ZQF0, ECO:0000269|PubMed:10498869, ECO:0000269|PubMed:11395493, ECO:0000269|PubMed:12773567, ECO:0000269|PubMed:21482717, ECO:0000269|PubMed:21659603, ECO:0000269|PubMed:21777809, ECO:0000269|PubMed:30898438, ECO:0000269|PubMed:35121901, ECO:0000269|PubMed:35597237, ECO:0000269|PubMed:35842428, ECO:0000269|PubMed:37165191, ECO:0000269|PubMed:37316668, ECO:0000269|PubMed:37674080}.
Interaction partners:
- ATR-interacting protein
- Cell cycle checkpoint control protein RAD9A
- TP53-binding protein 1
- Cell division control protein 45 homolog
- Fanconi anemia group J protein
- Treslin
- Breast cancer type 1 susceptibility protein
- BRCA1-associated RING domain protein 1
- Serine/threonine-protein kinase ATR
- Checkpoint protein HUS1
Sequence:
MSRNDKEPFFVKFLKSSDNSKCFFKALESIKEFQSEEYLQIITEEEALKIKENDRSLYICDPFSGVVFDHLKKLGCRIVGPQVVIFCMHHQRCVPRAEHPVYNMVMSDVTISCTSLEKEKREEVHKYVQMMGGRVYRDLNVSVTHLIAGEVGSKKYLVAANLKKPILLPSWIKTLWEKSQEKKITRYTDINMEDFKCPIFLGCIICVTGLCGLDRKEVQQLTVKHGGQYMGQLKMNECTHLIVQEPKGQKYECAKRWNVHCVTTQWFFDSIEKGFCQDESIYKTEPRPEAKTMPNSSTPTSQINTIDSRTLSDVSNISNINASCVSESICNSLNSKLEPTLENLENLDVSAFQAPEDLLDGCRIYLCGFSGRKLDKLRRLINSGGGVRFNQLNEDVTHVIVGDYDDELKQFWNKSAHRPHVVGAKWLLECFSKGYMLSEEPYIHANYQPVEIPVSHKPESKAALLKKKNSSFSKKDFAPSEKHEQADEDLLSQYENGSSTVVEAKTSEARPFNDSTHAEPLNDSTHISLQEENQSSVSHCVPDVSTITEEGLFSQKSFLVLGFSNENESNIANIIKENAGKIMSLLSRTVADYAVVPLLGCEVEATVGEVVTNTWLVTCIDYQTLFDPKSNPLFTPVPVMTGMTPLEDCVISFSQCAGAEKESLTFLANLLGASVQEYFVRKSNAKKGMFASTHLILKERGGSKYEAAKKWNLPAVTIAWLLETARTGKRADESHFLIENSTKEERSLETEITNGINLNSDTAEHPGTRLQTHRKTVVTPLDMNRFQSKAFRAVVSQHARQVAASPAVGQPLQKEPSLHLDTPSKFLSKDKLFKPSFDVKDALAALETPGRPSQQKRKPSTPLSEVIVKNLQLALANSSRNAVALSASPQLKEAQSEKEEAPKPLHKVVVCVSKKLSKKQSELNGIAASLGADYRWSFDETVTHFIYQGRPNDTNREYKSVKERGVHIVSEHWLLDCAQECKHLPESLYPHTYNPKMSLDISAVQDGRLCNSRLLSAVSSTKDDEPDPLILEENDVDNMATNNKESAPSNGSGKNDSKGVLTQTLEMRENFQKQLQEIMSATSIVKPQGQRTSLSRSGCNSASSTPDSTRSARSGRSRVLEALRQSRQTVPDVNTEPSQNEQIIWDDPTAREERARLASNLQWPSCPTQYSELQVDIQNLEDSPFQKPLHDSEIAKQAVCDPGNIRVTEAPKHPISEELETPIKDSHLIPTPQAPSIAFPLANPPVAPHPREKIITIEETHEELKKQYIFQLSSLNPQERIDYCHLIEKLGGLVIEKQCFDPTCTHIVVGHPLRNEKYLASVAAGKWVLHRSYLEACRTAGHFVQEEDYEWGSSSILDVLTGINVQQRRLALAAMRWRKKIQQRQESGIVEGAFSGWKVILHVDQSREAGFKRLLQSGGAKVLPGHSVPLFKEATHLFSDLNKLKPDDSGVNIAEAAAQNVYCLRTEYIADYLMQESPPHVENYCLPEAISFIQNNKELGTGLSQKRKAPTEKNKIKRPRVH