Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P16104 (H2AX)
 3,930 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chromatin structure has a crucial role in processes of metabolism, including transcription, DNA replication and DNA damage repair. An evolutionarily conserved variant of histone H2A, called H2AX, is one of the key components of chromatin. H2AX becomes rapidly phosphorylated on chromatin surrounding DNA double-strand breaks (DSBs). Recent studies have shown that H2AX and other components of damaged chromatin also become modified by acetylation and ubiquitylation. This review discusses how specific combinations of histone modifications affect the accumulation and function of DNA repair factors (MDC1, RNF8, RNF168, 53BP1, BRCA1) and chromatin remodeling complexes (INO80, SWR1, TIP60-p400) at DSBs. These collectively regulate DSB repair and checkpoint arrest, avoiding genomic instability and oncogenic transformation in higher eukaryotes.
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PMID:Crosstalk between histone modifications during the DNA damage response. 1934 39

Chromatin-modifying factors have essential roles in DNA processing pathways that dictate cellular functions. The ability of chromatin modifiers, including the INO80 and SWR1 chromatin-remodelling complexes, to regulate transcriptional processes is well established. However, recent studies reveal that the INO80 and SWR1 complexes have crucial functions in many other essential processes, including DNA repair, checkpoint regulation, DNA replication, telomere maintenance and chromosome segregation. During these diverse nuclear processes, the INO80 and SWR1 complexes function cooperatively with their histone substrates, gamma-H2AX and H2AZ. This research reveals that INO80 and SWR1 ATP-dependent chromatin remodelling is an integral component of pathways that maintain genomic integrity.
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PMID:Chromatin remodelling beyond transcription: the INO80 and SWR1 complexes. 1942 90

Manipulation of chromatin, in which genomic DNA is packaged, is a fundamental requirement for all DNA-based metabolic processes in eukayotic cells. Histone variant incorporation, histone post-translational modifications, and ATP-dependent chromatin remodeling are three major strategies for chromatin manipulation, and are relatively well characterized in transcriptional regulation. Emerging lines of evidence indicate that histone variants (H2AX and H2A.Z), histone post-translational modifications (acetylation, phosphorylation, methylation and ubiquitination) and chromatin-remodeling complexes (INO80, SWR1, SWI/SNF, RSC and NuRD) are important and direct players in the DNA double-strand break (DSB) response as well. New studies also reveal that incorporation of histone variants into nucleosomes, histone modifications and ATP-dependent chromatin remodeling are specifically and intimately connected during the DSB damage response. This article summarizes the recent advances in our understanding of the relationship between chromatin modifications and the DSB damage response.
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PMID:Chromatin response to DNA double-strand break damage. 2212 40