Faculty Opinions recommendation of The Histone Chaperones ASF1 and CAF-1 Promote MMS22L-TONSL-Mediated Rad51 Loading onto ssDNA during Homologous Recombination in Human Cells.
Year: 2018
Type: peer-review
Abstract: The access-repair-restore model for the role of chromatin in DNA repair infers that chromatin is a mere obstacle to DNA repair.However, here we show that blocking chromatin assembly, via knockdown of the histone chaperones ASF1A, CAF-1 or a mutation that prevents ASF1A binding to histones, hinders Rad51 loading onto ssDNA during homologous recombination.This is a consequence of reduced recruitment of the Rad51 loader MMS22L-TONSL to ssDNA, resulting in persistent RPA foci, extensive DNA end-resection, persistent activation of the ATR-Chk1 pathway and cell cycle arrest.In agreement, histones occupy ssDNA during DNA repair in yeast.We also uncovered DNA-PKcs-dependent DNA damage-induced ASF1A phosphorylation, which enhances chromatin assembly, promoting MMS22L-TONSL recruitment and hence Rad51 loading.We propose that transient assembly of newly-synthesized histones onto ssDNA serves to recruit MMS22L-TONSL to efficiently form the Rad51 nucleofilament for strand invasion, suggesting an active role of chromatin assembly in homologous recombination. dTOC BlurbHuang et al. show that the ASF1 and CAF-1 histone chaperones play active roles in DNA doublestrand break repair, by promoting the recruitment of MMS22L/TONSL to ssDNA to load Rad51 during homologous recombination in human cells.Furthermore, they show that histones occupy ssDNA during homologous recombination in yeast.
Author: John Tainer
Institution: The University of Texas MD Anderson Cancer Center
Language: English
Topic: DNA Repair Mechanisms
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Award: G1185003998
OpenAlex ID: W4245045119