Despite being the first homolog of the bacterial RecQ helicase to be identified in humans, the function of RECQL1 remains poorly characterized. Furthermore, unlike other members of the human RECQ family of helicases, mutations in RECQL1 have not been associated with a genetic disease. Here, we identify 2 families with a genome instability disorder that we have named RECON (RECql ONe) syndrome, caused by biallelic mutations in the RECQL gene. The affected individuals had short stature, progeroid facial features, a hypoplastic nose, xeroderma, and skin photosensitivity and were homozygous for the same missense mutation in RECQL1 (p.Ala459Ser), located within its zinc binding domain. Biochemical analysis of the mutant RECQL1 protein revealed that the p.A459S missense mutation compromised its ATPase, helicase, and fork restoration activity, while its capacity to promote single-strand DNA annealing was largely unaffected. At the cellular level, this mutation in RECQL1 gave rise to a defect in the ability to repair DNA damage induced by exposure to topoisomerase poisons and a failure of DNA replication to progress efficiently in the presence of abortive topoisomerase lesions. Taken together, RECQL1 is the fourth member of the RecQ family of helicases to be associated with a human genome instability disorder.

中文翻译：

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RECON 综合征是一种由 DNA 解旋酶 RECQL1 突变引起的基因组不稳定疾病

尽管是第一个在人类中发现的细菌 RecQ 解旋酶的同源物，但 RECQL1 的功能仍然没有得到很好的表征。此外，与人类 RECQ 解旋酶家族的其他成员不同，RECQL1 的突变与遗传疾病无关。在这里，我们确定了 2 个具有基因组不稳定性障碍的家族，我们将其命名为 RECON (RECql ONe) 综合征，由RECQL中的双等位基因突变引起基因。受影响的个体身材矮小、早老样面部特征、鼻子发育不全、干皮病和皮肤光敏性，并且是位于锌结合域内的 RECQL1 (p.Ala459Ser) 中相同错义突变的纯合子。突变 RECQL1 蛋白的生化分析显示 p.A459S 错义突变损害了其 ATP 酶、解旋酶和叉恢复活性，而其促进单链 DNA 退火的能力基本不受影响。在细胞水平上，RECQL1 中的这种突变导致修复因暴露于拓扑异构酶毒物而引起的 DNA 损伤的能力缺陷，以及在存在流产的拓扑异构酶损伤的情况下 DNA 复制无法有效进行。综合起来，