The Histone-Fold Protein CHRAC14 Influences Chromatin Composition in Response to DNA Damage

Abstract

Summary: Chromatin reorganization and the incorporation of specific histone modifications during DNA damage response are essential steps for the successful repair of any DNA lesion. Here, we show that the histone-fold protein CHRAC14 plays an essential role in response to DNA damage in Drosophila. Chrac14 mutants are hypersensitive to genotoxic stress and do not activate the G2/M cell-cycle checkpoint after damage induction. Even though the DNA damage repair process is activated in the absence of CHRAC14, lesions are not repaired efficiently. In the absence of CHRAC14, the centromere-specific histone H3 variant CENP-A localizes to sites of DNA damage, causing ectopic kinetochore formation and genome instability. CENP-A and CHRAC14 are able to interact upon damage. Our data suggest that CHRAC14 modulates chromatin composition in response to DNA damage, which is required for efficient DNA damage repair in Drosophila. : Chromatin reorganization in response to DNA damage is essential for successful repair. Mathew et al. report here that the histone-fold protein CHRAC14 is an essential player in the Drosophila DNA damage response. The absence of CHRAC14 causes inefficient DNA lesion repair and aberrant incorporation of the centromere-specific histone variant CENP-A, leading to ectopic kinetochores and genome instability. They further show that CENP-A and CHRAC14 interact upon damage, indicating complexity in the chromatin composition required for correct DNA damage repair.