DNA topoisomerase 2-binding protein 1 (DNA topoisomerase 2-beta-binding protein 1, TopBP1, KIAA0259)
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Function
- required for DNA replication
- role in rescue of stalled replication forks & checkpoint control
- binds double-stranded DNA breaks & nicks as well as single-stranded DNA
- recruits SWI/SNF chromatin remodeling complex to E2F1- responsive promoters
- down-regulates E2F1 activity & inhibits E2F1-dependent apoptosis during G1/S transition & after DNA damage
- induces kinase activity of ATR
- binds EDD, E2F1, PML, RAD9A, SMARCA2, SMARCA4 & POLE
- may interact with TOP2B
- phosphorylated on Ser & Thr in response to X-ray irradiation
- ubiquitinated & degraded by the proteasome
- X-ray irradiation reduces ubiquitination
Structure
- contains 8 BRCT domains
Compartment
- nucleus
- detected on unpaired autosomes in meiotic prophase cells.
- detected on X & Y chromosomes during later stages of prophase
- colocalizes with ATR & H2AFX at unsynapsed chromosome cores during prophase
- uniform nuclear distribution during G phase
- colocalizes with BRCA1 at stalled replication forks during S phase
- in mitotic cells, colocalizes with BRCA1 at spindle poles & centrosomes during metaphase & anaphase
- detected in discrete foci together with PML & numerous DNA repair enzymes after DNA damage by alkylating agents, UV or gamma irradiation
Expression
- expressed in heart, brain, placenta, lung, kidney
- up-regulated during the S phase of the cell cycle
- up-regulated by E2F1 & interferon