The histone chaperone SPT2 regulates chromatin structure and function in Metazoa.

Histone chaperones control nucleosome density and chromatin structure. In yeast, the H3-H4 chaperone Spt2 controls histone deposition at active genes but its roles in metazoan chromatin structure and organismal physiology are not known. Here we identify the Caenorhabditis elegans ortholog of SPT2 (CeSPT-2) and show that its ability to bind histones H3-H4 is important for germline development and transgenerational epigenetic gene silencing, and that spt-2 null mutants display signatures of a global stress response.

Ways to unwind with HROB, a new player in homologous recombination.

Homologous recombination (HR) is an important route for repairing DNA double-strand breaks (DSBs). The early stages of HR are well understood, but later stages remain mysterious. In this issue of , Hustedt and colleagues (pp.

H4K20me0 recognition by BRCA1-BARD1 directs homologous recombination to sister chromatids.

Genotoxic DNA double-strand breaks (DSBs) can be repaired by error-free homologous recombination (HR) or mutagenic non-homologous end-joining. HR supresses tumorigenesis, but is restricted to the S and G2 phases of the cell cycle when a sister chromatid is present. Breast cancer type 1 susceptibility protein (BRCA1) promotes HR by antagonizing the anti-resection factor TP53-binding protein 1(53BP1) (refs.

Tousled-like kinases stabilize replication forks and show synthetic lethality with checkpoint and PARP inhibitors.

DNA sequence and epigenetic information embedded in chromatin must be faithfully duplicated and transmitted to daughter cells during cell division. However, how chromatin assembly and DNA replication are integrated remains unclear. We examined the contribution of the Tousled-like kinases 1 and 2 (TLK1/TLK2) to chromatin assembly and maintenance of replication fork integrity.

H4K20me0 marks post-replicative chromatin and recruits the TONSL–MMS22L DNA repair complex.

After DNA replication, chromosomal processes including DNA repair and transcription take place in the context of sister chromatids. While cell cycle regulation can guide these processes globally, mechanisms to distinguish pre- and post-replicative states locally remain unknown. Here we reveal that new histones incorporated during DNA replication provide a signature of post-replicative chromatin, read by the human TONSL–MMS22L homologous recombination complex.

A unique binding mode enables MCM2 to chaperone histones H3-H4 at replication forks.

During DNA replication, chromatin is reassembled by recycling of modified old histones and deposition of new ones. How histone dynamics integrates with DNA replication to maintain genome and epigenome information remains unclear. Here, we reveal how human MCM2, part of the replicative helicase, chaperones histones H3-H4.