Abstract：
:The Bloom syndrome helicase BLM and topoisomerase-IIβ-binding protein 1 (TopBP1) are key regulators of genome stability. It was recently proposed that BLM phosphorylation on Ser338 mediates its interaction with TopBP1, to protect BLM from ubiquitylation and degradation (Wang et al., 2013). Here, we show that the BLM-TopBP1 interaction does not involve Ser338 but instead requires BLM phosphorylation on Ser304. Furthermore, we establish that disrupting this interaction does not markedly affect BLM stability. However, BLM-TopBP1 binding is important for maintaining genome integrity, because in its absence cells display increased sister chromatid exchanges, replication origin firing and chromosomal aberrations. Therefore, the BLM-TopBP1 interaction maintains genome stability not by controlling BLM protein levels, but via another as-yet undetermined mechanism. Finally, we identify critical residues that mediate interactions between TopBP1 and MDC1, and between BLM and TOP3A/RMI1/RMI2. Taken together, our findings provide molecular insights into a key tumor suppressor and genome stability network.
journal_name
Mol Celljournal_title
Molecular cellauthors
Blackford AN,Nieminuszczy J,Schwab RA,Galanty Y,Jackson SP,Niedzwiedz Wdoi
10.1016/j.molcel.2015.02.012subject
Has Abstractpub_date
2015-03-19 00:00:00pages
1133-1141issue
6eissn
1097-2765issn
1097-4164pii
S1097-2765(15)00104-5journal_volume
57pub_type
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