H2BK120ub and its reader RNF169 sequentially regulate replication fork remodeling and stability
Year: 2025
Type: article
Abstract: Ubiquitination of the C-terminus of histone H2B (H2BK120ub) is a key histone modification with functions in a wide array of DNA-related processes, best characterized in gene transcription and repair. A role for H2B ubiquitination in DNA replication has been postulated and investigated in yeast but is still elusive in human cells. Here, we uncovered a critical function of H2BK120ub in replication fork dynamics. H2BK120ub is present at replication forks and accumulates upon replication stress in a manner dependent on ATR and RAD51. Loss of RNF20, the main ubiquitin ligase promoting H2BK120ub, leads to RECQ1-mediated unrestrained replication fork progression and defective fork reversal upon mild replication stress, restoring fork stability in BRCA2-deficient cells. Furthermore, we identified RNF169, a factor involved in the DNA damage response and repair, as a reader of the H2BK120ub mark at stalled replication forks, where it is required to protect the nascent DNA from excessive nucleolytic degradation. Hence, RNF20, H2BK120ub and RNF169 are key novel players orchestrating replication stress response and fork plasticity in human cells.
Source: The EMBO Journal
Language: English
Topic: DNA Repair Mechanisms
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $7,990
Awards: G2107379357, Capturing in 3-D: chromatin mobilization upon replication stress, G2629240592, G3148817051, Mechanistic and functional understanding of the role of ubiquitin phosphorylation in genome stability, G4336179598, Deciphering the replication stress response at high resolution, in the context of nuclear architecture, Ubiquitin phosphorylation and the ubiquitin-like modifier ISG15 as novel modulators of genome stability and chemoresistance, G7213702007, G8165643995, G8690818240
OpenAlex ID: W4415648912