New histone incorporation marks sites of UV repair in human cells.
Chromatin organization is compromised during the repair of DNA damage. It remains unknown how and to what extent epigenetic information is preserved in vivo. A central question is whether chromatin reorganization involves recycling of parental histones or new histone incorporation. Here, we devise an approach to follow new histone deposition upon UV irradiation in human cells. We show that new H3.1 histones get incorporated in vivo at repair sites. Remarkably we find that H3.1, which is deposited during S phase, is also incorporated outside of S phase. Histone deposition is dependent on nucleotide excision repair (NER), indicating that it occurs at a postrepair stage. The histone chaperone chromatin assembly factor 1 (CAF-1) is directly involved in the histone deposition process in vivo. We conclude that chromatin restoration after damage cannot rely simply on histone recycling. New histone incorporation at repair sites both challenges epigenetic stability and possibly contributes to damage memory.
Polo
Sophie E
SE
Laboratory of Nuclear Dynamics and Genome Plasticity, UMR 218 CNRS/Institut Curie, 26 rue d'Ulm, 75248 Paris cedex 5, France.
Roche
Danièle
D
Almouzni
Geneviève
G
D002843:Chromatin / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000235:genetics; D006367:HeLa Cells; D006388:Hemagglutinins / Q000737:chemistry; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D034741:RNA, Small Interfering / Q000737:chemistry / Q000378:metabolism; D014162:Transfection; D014466:Ultraviolet Rays
D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006388:Hemagglutinins; D006657:Histones; D018809:Proliferating Cell Nuclear Antigen; D034741:RNA, Small Interfering