CHD1L maintains genome integrity by facilitating okazaki fragment maturation - PubMed
4 hours ago
- #genome integrity
- #Okazaki fragment maturation
- #CHD1L
- The study identified CHD1L as a critical modulator of Okazaki fragment maturation, essential for maintaining genome integrity.
- CHD1L loss is synthetic lethal with severe PARG inhibition, leading to toxic pADPr accumulation in S-phase cells from unprocessed Okazaki fragments.
- Both the ATPase and pADPr-binding macrodomain of CHD1L are required to prevent this toxic pADPr accumulation.
- CHD1L deficiency causes persistent retention of SSB repair factors and E3 ubiquitin ligases, challenging prior models of limited chromatin accessibility.
- The findings establish a novel housekeeping role for CHD1L in facilitating efficient turnover of DNA repair factors at replication-associated SSBs.