scholarly journals Regulation of Telomere Structure and Functions by Subunits of the INO80 Chromatin Remodeling Complex

2007 ◽  
Vol 27 (16) ◽  
pp. 5639-5649 ◽  
Author(s):  
Eun Young Yu ◽  
Olga Steinberg-Neifach ◽  
Alain T. Dandjinou ◽  
Frances Kang ◽  
Ashby J. Morrison ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Position Effect ◽  
Strand Break ◽  
Telomere Maintenance ◽  
Regulation Of Transcription ◽  
Chromatin Remodeling Complex ◽  
Dna Double Strand Break ◽  
Preferential Localization ◽  
Chromatin Remodeling Complexes ◽  
Tetratricopeptide Repeat Domain

ABSTRACT ATP-dependent chromatin remodeling complexes have been implicated in the regulation of transcription, replication, and more recently DNA double-strand break repair. Here we report that the Ies3p subunit of the Saccharomyces cerevisiae INO80 chromatin remodeling complex interacts with a conserved tetratricopeptide repeat domain of the telomerase protein Est1p. Deletion of IES3 and some other subunits of the complex induced telomere elongation and altered telomere position effect. In telomerase-negative mutants, loss of Ies3p delayed the emergence of recombinational survivors and stimulated the formation of extrachromosomal telomeric circles in survivors. Deletion of IES3 also resulted in heightened levels of telomere-telomere fusions in telomerase-deficient strains. In addition, a delay in survivor formation was observed in an Arp8p-deficient mutant. Because Arp8p is required for the chromatin remodeling activity of the INO80 complex, the complex may promote recombinational telomere maintenance by altering chromatin structure. Consistent with this notion, we observed preferential localization of multiple subunits of the INO80 complex to telomeres. Our results reveal novel functions for a subunit of the telomerase complex and the INO80 chromatin remodeling complex.

INO80 requires a polycomb subunit to regulate the establishment of poised chromatin in murine spermatocytes

Development ◽  
2022 ◽  
Vol 149 (1) ◽  
Author(s):  
Prabuddha Chakraborty ◽  
Terry Magnuson
Keyword(s):  
Chromatin Remodeling ◽  
Binding Sites ◽  
Strand Break ◽  
Rna Seq ◽  
Genome Wide Analysis ◽  
The Core ◽  
Chromatin Remodeling Complex ◽  
Genome Wide ◽  
Dna Double Strand Break ◽  
Transcription Program

ABSTRACT INO80 is the catalytic subunit of the INO80-chromatin remodeling complex that is involved in DNA replication, repair and transcription regulation. Ino80 deficiency in murine spermatocytes (Ino80cKO) results in pachytene arrest of spermatocytes due to incomplete synapsis and aberrant DNA double-strand break repair, which leads to apoptosis. RNA-seq on Ino80cKO spermatocytes revealed major changes in transcription, indicating that an aberrant transcription program arises upon INO80 depletion. In Ino80WT spermatocytes, genome-wide analysis showed that INO80-binding sites were mostly promoter proximal and necessary for the regulation of spermatogenic gene expression, primarily of premeiotic and meiotic genes. Furthermore, most of the genes poised for activity, as well as those genes that are active, shared INO80 binding. In Ino80cKO spermatocytes, most poised genes demonstrated de-repression due to reduced H3K27me3 enrichment and, in turn, showed increased expression levels. INO80 interacts with the core PRC2 complex member SUZ12 and promotes its recruitment. Furthermore, INO80 mediates H2A.Z incorporation at the poised promoters, which was reduced in Ino80cKO spermatocytes. Taken together, INO80 is emerging as a major regulator of the meiotic transcription program by mediating poised chromatin establishment through SUZ12 binding.

scholarly journals Schizosaccharomyces pombe KAT5 contributes to resection and repair of a DNA double strand break

Genetics ◽  
2021 ◽  
Author(s):  
Tingting Li ◽  
Ruben C Petreaca ◽  
Susan L Forsburg
Keyword(s):  
Dna Damage ◽  
Homologous Recombination ◽  
Chromatin Remodeling ◽  
Dna Damage Response ◽  
Histone Acetyltransferase ◽  
Strand Break ◽  
Double Strand Break ◽  
Dna Damage Checkpoint ◽  
Dna Double Strand Break ◽  
Damage Response

Abstract Chromatin remodeling is essential for effective repair of a DNA double strand break. KAT5 (S. pombe Mst1, human TIP60) is a MYST family histone acetyltransferase conserved from yeast to humans that coordinates various DNA damage response activities at a DNA double strand break (DSB), including histone remodeling and activation of the DNA damage checkpoint. In S. pombe, mutations in mst1+ causes sensitivity to DNA damaging drugs. Here we show that Mst1 is recruited to DSBs. Mutation of mst1+ disrupts recruitment of repair proteins and delays resection. These defects are partially rescued by deletion of pku70, which has been previously shown to antagonize repair by homologous recombination. These phenotypes of mst1 are similar to pht1-4KR, a non-acetylatable form of histone variant H2A.Z, which has been proposed to affect resection. Our data suggest that Mst1 functions to direct repair of DSBs towards homologous recombination pathways by modulating resection at the double strand break.

scholarly journals DNA Damage-Induced Phosphorylation of TRF2 Is Required for the Fast Pathway of DNA Double-Strand Break Repair

2009 ◽  
Vol 29 (13) ◽  
pp. 3597-3604 ◽  
Author(s):  
Nazmul Huda ◽  
Hiromi Tanaka ◽  
Marc S. Mendonca ◽  
David Gilley
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Functional Role ◽  
Strand Break ◽  
Telomere Maintenance ◽  
Telomeric Dna ◽  
Dsb Repair ◽  
Dna Double Strand Break ◽  
Damage Response ◽  
Fast Pathway

ABSTRACT Protein kinases of the phosphatidylinositol 3-kinase-like kinase family, originally known to act in maintaining genomic integrity via DNA repair pathways, have been shown to also function in telomere maintenance. Here we focus on the functional role of DNA damage-induced phosphorylation of the essential mammalian telomeric DNA binding protein TRF2, which coordinates the assembly of the proteinaceous cap to disguise the chromosome end from being recognized as a double-stand break (DSB). Previous results suggested a link between the transient induction of human TRF2 phosphorylation at threonine 188 (T188) by the ataxia telangiectasia mutated protein kinase (ATM) and the DNA damage response. Here, we report evidence that X-ray-induced phosphorylation of TRF2 at T188 plays a role in the fast pathway of DNA DSB repair. These results connect the highly transient induction of human TRF2 phosphorylation to the DNA damage response machinery. Thus, we find that a protein known to function in telomere maintenance, TRF2, also plays a functional role in DNA DSB repair.

scholarly journals Opposing ISWI- and CHD-class chromatin remodeling activities orchestrate heterochromatic DNA repair

2014 ◽  
Vol 207 (6) ◽  
pp. 717-733 ◽  
Author(s):  
Karolin Klement ◽  
Martijn S. Luijsterburg ◽  
Jordan B. Pinder ◽  
Chad S. Cena ◽  
Victor Del Nero ◽  
...  
Keyword(s):  
Dna Repair ◽  
Dna Replication ◽  
Chromatin Remodeling ◽  
Somatic Mutation ◽  
Strand Break ◽  
Dsb Repair ◽  
Nucleosome Remodeling ◽  
Dna Double Strand Break ◽  
Recruitment System ◽  
Chromatin Relaxation

Heterochromatin is a barrier to DNA repair that correlates strongly with elevated somatic mutation in cancer. CHD class II nucleosome remodeling activity (specifically CHD3.1) retained by KAP-1 increases heterochromatin compaction and impedes DNA double-strand break (DSB) repair requiring Artemis. This obstruction is alleviated by chromatin relaxation via ATM-dependent KAP-1S824 phosphorylation (pKAP-1) and CHD3.1 dispersal from heterochromatic DSBs; however, how heterochromatin compaction is actually adjusted after CHD3.1 dispersal is unknown. In this paper, we demonstrate that Artemis-dependent DSB repair in heterochromatin requires ISWI (imitation switch)-class ACF1–SNF2H nucleosome remodeling. Compacted chromatin generated by CHD3.1 after DNA replication necessitates ACF1–SNF2H–mediated relaxation for DSB repair. ACF1–SNF2H requires RNF20 to bind heterochromatic DSBs, underlies RNF20-mediated chromatin relaxation, and functions downstream of pKAP-1–mediated CHD3.1 dispersal to enable DSB repair. CHD3.1 and ACF1–SNF2H display counteractive activities but similar histone affinities (via the plant homeodomains of CHD3.1 and ACF1), which we suggest necessitates a two-step dispersal and recruitment system regulating these opposing chromatin remodeling activities during DSB repair.

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