# TORC2 is required for the accumulation of γH2A in response to DNA damage

## TL;DR

This study shows that TORC2 signaling is essential for γH2A accumulation in response to DNA damage in fission yeast.

## Contribution

The study reveals that TORC2-Gad8 signaling directly regulates γH2A accumulation, linking TOR signaling to DNA damage response.

## Key findings

- TORC2-Gad8 signaling is required for γH2A accumulation in response to DNA damage.
- The effect of TORC2 on γH2A is immediate, not adaptive, as shown using Torin1.
- Deleting chromatin regulators like Paf1C or SAGA components restores γH2A in TORC2-deficient cells.

## Abstract

TOR protein kinases serve as the catalytic subunit of the TORC1 and TORC2 complexes, which regulate cellular growth, proliferation, and survival. In the fission yeast, Schizosaccharomyces pombe, cells lacking TORC2 or its downstream kinase Gad8 (AKT or SGK1 in human cells) exhibit sensitivity to a wide range of stress conditions, including DNA damage stress. One of the first responses to DNA damage is the phosphorylation of C-terminal serine residues within histone H2AX in human cells (γH2AX), or histone H2A in yeast cells (γH2A). The kinases responsible for γH2A in S. pombe are the two DNA damage checkpoint kinases Rad3 and Tel1 (ATR and ATM, respectively, in human cells). Here we report that TORC2-Gad8 signaling is required for accumulation of γH2A in response to DNA damage and during quiescence. Using the TOR-specific inhibitor, Torin1, we demonstrate that the effect of TORC2 on γH2A in response to DNA damage is immediate, rather than adaptive. The lack of γH2A is restored by deletion mutations of transcription and chromatin modification factors, including loss of components of Paf1C, SAGA, Mediator, and the bromo-domain proteins Bdf1/Bdf2. Thus, we suggest that TORC2-Gad8 may affect the accumulation of γH2A by regulating chromatin structure and function.