Chromosome Biology: Controlling CENPA Mislocalization

RESEARCH HIGHLIGHTS

Nature Reviews Molecular Cell Biology | AOP, published online 30 April 2014; doi:10.1038/nrm3804

CHROMOSOME BIOLOGY chromosomes and anaphase bridges, lagging chromosomes and chromo somal breaks. Thus, mutating or Controlling CENPA mislocalization depleting Chrac14 causes CENPA mislocalization and ectopic kineto chromatin misincorporation. chore formation, and results in Althogh Chrac14‑mutant flies seem chromosome segregation defects. normal, exposing their larvae to Whereas CENPA is not ionizing radiation causes severe recruited to DNA lesions in normal developmental defects and high cells, inducing DNA damage in mortality. In tissues of irradiated Chrac14‑depleted cells resulted in a Chrac14‑mutant flies, damaged cells significant increase in the colocaliza- fail to activate the G2/M checkpoint tion of the phosphorylated histone and proceed to mitosis. Furthermore, variant H2Av (a marker of DNA in Chrac14‑depleted fly S2 cells, damage) and CENPA nuclear foci, DNA damage repair kinetics are which indicates that Chrac14 may noticeably attenuated. This indicates prevent CENPA deposition at DNA NPG that Chrac14 has a role in the DNA lesions. In support of this, the authors The specific deposition of the damage response. found that both proteins interact in centromere-specific histone variant The depletion of Chrac14 in S2 embryos after irradiation. Based on centromere protein A (CENPA) is cells also resulted in a significant their findings, they propose that dur- key for proper kinetochore assembly increase in the number of CENPA ing DNA damage repair nucleosomes and chromosome segregation. immunofluorescence foci (also are formed using the available Erhardt and colleagues report that observed in Chrac14‑mutant histone pool, including variants mutating or in Drosophila melanogaster, the embryos), which is indicative of such as CENPA. Misincorporation histone‑fold protein Chromatin ectopic CENPA incorporation into of CENPA can lead to ectopic depleting accessibility complex 14 kD (Chrac14) chromatin, and caused ectopic kinetochore formation, and this is Chrac14 interacts with CENPA, regulates its kinetochore assembly, which was prevented and/or corrected by a causes … chromatin localization after DNA evident by CENPA foci colocalization Chrac14‑dependent mechanism. damage and prevents aneuploidy. with kinetochore proteins. Mitotic Eytan Zlotorynski ectopic Chrac14 associates with spreads from Chrac14‑depleted kinetochore several chromatin remodelling cells or Chrac14‑mutant embryos ORIGINAL RESEARCH PAPER Mathew, V. et al. The histone-fold protein CHRAC14 influences formation complexes and was identified by showed multiple CENPA foci per chromatin composition in response to DNA the authors in a genetic screen as chromosome and, consequently, damage. Cell Rep. http://dx.doi.org/10.1016/j. a candidate modulator of CENPA mitotic defects, such as dicentric celrep.2014.03.008 (2014)

NATURE REVIEWS | MOLECULAR CELL BIOLOGY VOLUME 15 | JUNE 2014