AI Article Synopsis
- The histone chaperone complex FACT, made up of SPT16 and SSRP1, is important for DNA processes like replication, transcription, and repair, but its specific roles are not fully understood.
- Research shows that human SPT16 is modified by ubiquitin at lysine-674 (K674), which inhibits its binding to histones H3.1-H4, an interaction critical for its function.
- Cells with a specific K674R mutation in SPT16 displayed lower SPT16 ubiquitylation, less histone H3.1 in chromatin, slower growth, and greater difficulty during DNA replication, suggesting that SPT16's ubiquitylation impacts its histone-binding ability and
Article Abstract
The histone chaperone complex FACT comprises SPT16 and SSRP1 and contributes to DNA replication, transcription, and repair, but how it plays such various roles is unclear. Here, we show that human SPT16 is ubiquitylated at lysine-674 (K674) by the DCAF14-CRL4 ubiquitin ligase. K674 is located in the middle domain of SPT16, and the corresponding residue of the yeast ortholog is critical for binding to histone H3.1-H4. We show that the middle domain of human SPT16 binds to histone H3.1-H4 and that this binding is inhibited by K674 ubiquitylation. Cells with heterozygous knockin of a K674R mutant of SPT16 manifest reduction of both SPT16 ubiquitylation and H3.1 in chromatin, a reduced population in mid S phase, impaired proliferation, and increased susceptibility to S phase stress. Our data thus indicate that SPT16 ubiquitylation by DCAF14-CRL4 regulates FACT binding to histones and may thereby control DNA replication-coupled histone incorporation into chromatin.
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| http://dx.doi.org/10.1016/j.celrep.2022.110541 | DOI Listing |
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