Function of the histone N-terminal acetyltransferase Naa40 in DNA damage response

ABSTRACT: N-alpha-acetyltransferase 40 (NAA40) catalyzes acetylation on the N-terminal tip of histones H4 (N-acH4) and H2A (N-acH2A) harboring the Ser(1)-Gly(2)-Arg(3)-Gly(4) recognition sequence. In addition to the well-known role of N-terminal acetylation in protein degradation and stability, recent studies have reported the regulatory function of NAA40 and its associated histone N-terminal acetylation in different cancer types. The H2A.X histone variant, which has a critical role in DNA damage and repair, also carries the N-terminal recognition motif ‘SGRG’ at its N-terminus and could be therefore subjected to N-terminal acetylation by NAA40 (Magin et al., 2015). Prior to DNA damage, H2A.X is continuously subjected to proteasomal degradation, whereas upon the formation of double strand breaks (DSBs) is rapidly stabilized. Once incorporated into chromatin, H2A.X is phosphorylated at serine 139 (γΗ2Α.Χ) to generate γH2A.X foci that play a key role in the amplification of the DNA damage signal and the recruitment of the DNA damage checkpoint and repair machinery (Atsumi et al., 2015). Although γΗ2Α.Χ is essential in the DNA Damage Response (DDR) process, the existence and function of other marks on histone H2A.X are largely overlooked. We hypothesize that H2A.X could be a new substrate for NAA40 and that H2A.X N-terminal acetylation (N-acH2A.X) could be involved in DDR by either influencing chromatin accessibility and the recruitment of downstream DDR factors or by serving as a degradation signal (Ac/N-degron) for this histone variant (Nguyen et al., 2018). Hence, in the current study we investigated the possible N-terminal acetylation of histone H2A.X.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Roberta Noberini  

LAB HEAD: Tiziana Bonaldi

PROVIDER: PXD050981 | Pride | 2025-07-21

REPOSITORIES: Pride