RIF1-ASF1-mediated high-order chromatin structure safeguards genome integrity.

Autor: Feng S; State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 100871, Beijing, China., Ma S; State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 100871, Beijing, China., Li K; State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 100871, Beijing, China., Gao S; State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 100871, Beijing, China., Ning S; State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 100871, Beijing, China., Shang J; State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 100871, Beijing, China., Guo R; State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 100871, Beijing, China., Chen Y; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, 100871, Beijing, China., Blumenfeld B; Department of Microbiology and Molecular Genetics, Institute of Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University, Jerusalem, 91120, Israel., Simon I; Department of Microbiology and Molecular Genetics, Institute of Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University, Jerusalem, 91120, Israel., Li Q; State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 100871, Beijing, China.; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, 100871, Beijing, China., Guo R; State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 100871, Beijing, China., Xu D; State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 100871, Beijing, China. xudongyi@pku.edu.cn.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Feb 17; Vol. 13 (1), pp. 957. Date of Electronic Publication: 2022 Feb 17.
DOI: 10.1038/s41467-022-28588-y
Abstrakt: The 53BP1-RIF1 pathway antagonizes resection of DNA broken ends and confers PARP inhibitor sensitivity on BRCA1-mutated tumors. However, it is unclear how this pathway suppresses initiation of resection. Here, we identify ASF1 as a partner of RIF1 via an interacting manner similar to its interactions with histone chaperones CAF-1 and HIRA. ASF1 is recruited to distal chromatin flanking DNA breaks by 53BP1-RIF1 and promotes non-homologous end joining (NHEJ) using its histone chaperone activity. Epistasis analysis shows that ASF1 acts in the same NHEJ pathway as RIF1, but via a parallel pathway with the shieldin complex, which suppresses resection after initiation. Moreover, defects in end resection and homologous recombination (HR) in BRCA1-deficient cells are largely suppressed by ASF1 deficiency. Mechanistically, ASF1 compacts adjacent chromatin by heterochromatinization to protect broken DNA ends from BRCA1-mediated resection. Taken together, our findings identify a RIF1-ASF1 histone chaperone complex that promotes changes in high-order chromatin structure to stimulate the NHEJ pathway for DSB repair.
(© 2022. The Author(s).)
Databáze: MEDLINE
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