Role of H2AX in DNA damage response and human cancers.
H2AX, the evolutionarily conserved variant of histone H2A, has been identified as one of the key histones to undergo various post-translational modifications in response to DNA double-strand breaks (DSBs). By virtue of these modifications, that include acetylation, phosphorylation and ubiquitination, H2AX marks the damaged DNA double helix, facilitating local recruitment and retention of DNA repair and chromatin remodeling factors to restore genomic integrity. These modifications are essential for effective DSB repair, so is their removal for cell, to recover from checkpoint arrest. Because of these vital roles during DSB signaling and also its activation during early cancer stages, H2AX is emerging as an intriguing gene in tumor biology, supported further by frequent deletion of the region harboring this gene. This review focuses on the insights gained from recent studies on dynamic regulation of H2AX in DSB repair. Also, posing future challenges in the area of chromatin reorganization and retention of epigenetic signature post-DSB-repair with implication of its haploinsufficiency in human cancers.
Srivastava
Niloo
N
National Centre of Applied Human Genetics, School of Life Sciences, Jawaharlal Nehru University (JNU), Aruna Asafali Marg, New Delhi 110067, India.
Gochhait
Sailesh
S
National Centre of Applied Human Genetics, School of Life Sciences, Jawaharlal Nehru University (JNU), Aruna Asafali Marg, New Delhi 110067, India.
de Boer
Peter
P
Department of Obstetrics and Gynaecology, Radboud University Nijmegen Medical Centre, The Netherlands.
Bamezai
Rameshwar N K
RNK
National Centre of Applied Human Genetics, School of Life Sciences, Jawaharlal Nehru University (JNU), Aruna Asafali Marg, New Delhi 110067, India. Electronic address: bame0200@mail.jnu.ac.in.
D004249:DNA Damage; D006657:Histones / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D011499:Protein Processing, Post-Translational
C468783:H2AX protein, human; D006657:Histones