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Acetylation of histone n-terminal tails contributes to DNA double strand break repair

Qin, Song
http://rave.ohiolink.edu/etdc/view?acc_num=osu1134575402

Abstract Details

2006, Doctor of Philosophy, Ohio State University, Molecular, Cellular, and Developmental Biology.
Acetylation of the N-terminal tails of newly synthesized histones H3 and H4 by type-B histone acetyltransferases (HATs) is thought to play a role in chromatin assembly. While originally known as a cytoplasmic factor, Hat1p, the catalytic subunit of the first identified type-B HAT, has been shown to exist in both the cytoplasm and the nucleus. Hat1p and specific lysine residues in the histone H3 N-terminal tail have been shown to be redundantly required for telomeric silencing, and multiple protein factors have been found to be involved in both telomeric silencing and DNA damage repair. This raised the possibility that Hat1p might also be involved in DNA damage repair. Substitution of specific lysine residues in the histone H3 N-terminal tail, as well as combination of specific lysine residue replacement in H3 and HAT1 deletion resulted in enhanced sensitivity to methyl methanesulfonate. This sensitivity was specific for DNA double Strand beraks (DSBs), as these mutants were sensitive to endonuclease digestion, but not to UV irradiation. While histone H3 mutations showed minor effects on nonhomologous end joining, the primary defect in the histone H3 and HAT1 mutants was in pathway of homologous recombination. Subsequent epistasis analysis indicates that the histone H3 and Hat1p may contribute to DSB repair through an Asf1p-dependent chromatin assembly pathway. Hat1p was then found to become associated with damaged DNA. Further kinetic analysis showed that Hat1p localization to DSB occurs after the phosphorylation of histone H2A S129 and concomitantly with the recruitment of the recombinational repair factor Rad52p. In addition, the nuclear Hat1p-associated histone chaperonee Hif1p was also recruited to DSB and followed similar kenetics as that of Hat1p. Moreover, the acetylation of all four histone H4 N-terminal domain lysine residues including 5, 8, 12 and 16 was increased following DSB generation on the MAT locus, but only acetylation of lysine 12, the primary target of Hat1p, is dependent on the presence of Hat1p. The results presented here suggest that Hat1p is responsible for specific changes in histone modification that occur during the course of recombinational repair of DSB and thus plays a direct role in DSB repair.
Mark Parthun (Advisor)
112 p.
Biology, Molecular
HISTONE; Hat1p; histones H3; DNA; chromatin; HAT1; DSBs

Recommended Citations

Citations

  • Qin, S. (2006). Acetylation of histone n-terminal tails contributes to DNA double strand break repair [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1134575402

    APA Style (7th edition)

  • Qin, Song. Acetylation of histone n-terminal tails contributes to DNA double strand break repair. 2006. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1134575402.

    MLA Style (8th edition)

  • Qin, Song. "Acetylation of histone n-terminal tails contributes to DNA double strand break repair." Doctoral dissertation, Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=osu1134575402

    Chicago Manual of Style (17th edition)

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This open access ETD is published by The Ohio State University and OhioLINK.