title: Dynamic alteration in H3 serine 10 phosphorylation is G1-phase specific during ionization radiation induced DNA damage response in human cells.
abstract: Chromatin acts as a natural barrier in DNA-damage recognition and repair. Histones undergo differential post-translational modification(s) to facilitate DNA damage response (DDR). Importance of modifications like phosphorylation of histone variant H2A.X in DNA repair is very well understood, however, ambiguous results exist in literature regarding the levels of certain histone modifications and their possible role in repair. In the present study, we have investigated in depth the alteration in the level of the highly dynamic histone mark H3S10P as it plays a dual role in different phases of the cell cycle. We show here that H3S10P decreases specifically from irradiated G1-enriched cells irrespective of the damaging agent or the cell line used in the study. Interestingly, the loss occurs predominantly from H3.3 variant which is a transcription activation mark like H3S10P itself, suggesting that the alteration might be implicated in transcription repression. The decrease in other transcription marks like H3K9Ac, H3K14Ac, H3K56Ac and H3S28P along with the occurrence of chromatin condensation in response to DNA damage in G1 phase strengthens the hypothesis. In addition, the alteration in the level of H3S10P shows an inverse correlation with that of γH2AX in a dose-dependent manner and probably occurs from the same mononucleosome. We propose that the drop in the levels of histone H3S10 phosphorylation is a universal phenomenon in response to DNA damage and is a trigger to induce transcription repressive state to facilitate repair.
authors.affiliation: Epigenetics and Chromatin Biology Group, Gupta Lab, Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410210, MH, India.
authors.forename: Ajit K
authors.initials: AK
authors.lastname: Sharma
authors.affiliation: Epigenetics and Chromatin Biology Group, Gupta Lab, Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410210, MH, India.
authors.forename: Saikat
authors.initials: S
authors.lastname: Bhattacharya
authors.affiliation: Epigenetics and Chromatin Biology Group, Gupta Lab, Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410210, MH, India.
authors.forename: Shafqat A
authors.initials: SA
authors.lastname: Khan
authors.affiliation: Epigenetics and Chromatin Biology Group, Gupta Lab, Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410210, MH, India.
authors.forename: Bharat
authors.initials: B
authors.lastname: Khade
authors.affiliation: Epigenetics and Chromatin Biology Group, Gupta Lab, Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410210, MH, India. Electronic address: sgupta@actrec.gov.in.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Gupta
mesh_terms: D002478:Cells, Cultured; D004249:DNA Damage; D016193:G1 Phase; D005720:Gamma Rays; D006657:Histones / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D009707:Nucleosomes / Q000378:metabolism; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism
chemical_list: C468783:H2AX protein, human; D006657:Histones; D009707:Nucleosomes; D012694:Serine
keywords: Cell cycle; Chromatin; DNA damage response; G1 phase; H3 serine 10 phosphorylation; Ionizing radiation