H2AFX

Histone H2A.x ;
H2a/x ;

developmental stage:Synthesized in G1 as well as in S-phase. ,domain:The [ST]-Q motif constitutes a recognition sequence for kinases from the PI3/PI4-kinase family. ,function:Variant histone H2A which replaces conventional H2A in a subset of nucleosomes. Nucleosomes wrap and compact DNA into chromatin , limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation , DNA repair , DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones , also called histone code , and nucleosome remodeling. Required for checkpoint-mediated arrest of cell cycle progression in response to low doses of ionizing radiation and for efficient repair of DNA double strand breaks (DSBs) specifically when modified by C-terminal phosphorylation. ,PTM:Monoubiquitination of Lys-120 (H2AXK119ub) by RING1 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression. Following DNA double-strand breaks (DSBs) , it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168 , leading to the recruitment of repair proteins to sites of DNA damage. Monoubiquitination and ionizing radiation-induced 'Lys-63'-linked ubiquitination are distinct events. ,PTM:Phosphorylated on Ser-140 (to form gamma-H2AFX or H2AX139ph) in response to DNA double strand breaks (DSBs) generated by exogenous genotoxic agents and by stalled replication forks , and may also occur during meiotic recombination events and immunoglobulin class switching in lymphocytes. Phosphorylation can extend up to several thousand nucleosomes from the actual site of the DSB and may mark the surrounding chromatin for recruitment of proteins required for DNA damage signaling and repair. Widespread phosphorylation may also serve to amplify the damage signal or aid repair of persistent lesions. Phosphorylation of Ser-140 (H2AX139ph) in response to ionizing radiation is mediated by both ATM and PRKDC while defects in DNA replication induce Ser-140 phosphorylation (H2AX139ph) subsequent to activation of ATR and PRKDC. Dephosphorylation of Ser-140 by PP2A is required for DNA DSB repair. In meiosis , Ser-140 phosphorylation (H2AX139ph) may occur at synaptonemal complexes during leptotene as an ATM-dependent response to the formation of programmed DSBs by SPO11. Ser-140 phosphorylation (H2AX139ph) may subsequently occurs at unsynapsed regions of both autosomes and the XY bivalent during zygotene , downstream of ATR and BRCA1 activation. Ser-140 phosphorylation (H2AX139ph) may also be required for transcriptional repression of unsynapsed chromatin and meiotic sex chromosome inactivation (MSCI) , whereby the X and Y chromosomes condense in pachytene to form the heterochromatic XY-body. During immunoglobulin class switch recombination in lymphocytes , Ser-140 phosphorylation (H2AX139ph) may occur at sites of DNA-recombination subsequent to activation of the activation-induced cytidine deaminase AICDA. Phosphorylation at Tyr-143 (H2AXY142ph) by BAZ1B/WSTF determines the relative recruitment of either DNA repair or pro-apoptotic factors. Phosphorylation at Tyr-143 (H2AXY142ph) favors the recruitment of APBB1/FE65 and pro-apoptosis factors such as MAPK8/JNK1 , triggering apoptosis. In contrast , dephosphorylation of Tyr-143 by EYA proteins (EYA1 , EYA2 , EYA3 or EYA4) favors the recruitment of MDC1-containing DNA repair complexes to the tail of phosphorylated Ser-140 (H2AX139ph) . ,similarity:Belongs to the histone H2A family. ,subunit:The nucleosome is a histone octamer containing two molecules each of H2A , H2B , H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. Interacts with numerous proteins required for DNA damage signaling and repair when phosphorylated on Ser-140. These include MDC1 , TP53BP1 , BRCA1 and the MRN complex , composed of MRE11A , RAD50 , and NBN. Interaction with the MRN complex is mediated at least in part by NBN. Also interacts with DHX9/NDHII when phosphorylated on Ser-140. ,

cell cycle checkpoint , DNA damage checkpoint , M phase , double-strand break repair via homologous recombination ,recombinational repair , DNA metabolic process , DNA repair , regulation of DNA repair , double-strand break repair , DNA recombination , DNA packaging , chromatin organization , chromatin assembly or disassembly , nucleosome assembly ,response to DNA damage stimulus , cell cycle , meiosis , intracellular signaling cascade , gamete generation ,spermatogenesis , response to radiation , response to abiotic stimulus , response to ionizing radiation , positive regulation of macromolecule metabolic process , sexual reproduction , cell cycle process , cell cycle phase , chromatin assembly , DNA integrity checkpoint , multicellular organism reproduction , cellular response to stress , cellular macromolecular complex subunit organization , cellular macromolecular complex assembly , nucleosome organization ,DNA damage response , signal transduction , macromolecular complex subunit organization , positive regulation of DNA repair , positive regulation of nucleobase , nucleoside , nucleotide and nucleic acid metabolic process , male gamete generation , positive regulation of response to stimulus , reproductive process in a multicellular organism , regulation of DNA metabolic process , positive regulation of DNA metabolic process , positive regulation of nitrogen compound metabolic process , chromosome organization , meiotic cell cycle , M phase of meiotic cell cycle , regulation of cell cycle ,macromolecular complex assembly , protein-DNA complex assembly , regulation of cellular response to stress ,

Nucleus . Chromosome .