Role of HP1β during spermatogenesis and DNA replication

Maintaining genomic stability in a continually dividing cell population requires accurate DNA repair, especially in male germ cells. Repair and replication protein access to DNA, however, is complicated by chromatin compaction. The HP1β chromatin protein, encoded by Cbx1 , is associated with chromatin condensation but its role in meiosis is not clear. To investigate the role of Cbx 1 in male germ cells, we generated testis specific Cbx 1 deficient transgenic mice by crossing Cbx 1flox/flox ( Cbx 1f/f) mice with Stra8 Cre +/− mice. Loss of Cbx 1 in testes adversely affected sperm maturation and Cbx 1 deletion increased seminiferous tubule degeneration and basal level DNA damage., We observed that Cbx 1−/− MEF cells displayed reduced resolution of stalled DNA replication forks as well as decreased fork restart, indicating defective DNA synthesis. Taken together, these results suggest that loss of Cbx 1 in growing cells leads to DNA replication defects and associated DNA damage that impact cell survival.