DDX11

DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which is an enzyme that possesses both ATPase and DNA helicase activities. This gene is a homolog of the yeast CHL1 gene, and may function to maintain chromosome transmission fidelity and genome stability. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq]

DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 11 (CHL1-like helicase homolog, S. cerevisiae)

DNA-dependent ATPase and ATP-dependent DNA helicase that participates in various functions in genomic stability, including DNA replication, DNA repair and heterochromatin organization as well as in ribosomal RNA synthesis (PubMed:10648783, PubMed:21854770, PubMed:23797032, PubMed:26089203, PubMed:26503245).

Its double-stranded DNA helicase activity requires either a minimal 5'-single-stranded tail length of approximately 15 nt (flap substrates) or 10 nt length single-stranded gapped DNA substrates of a partial duplex DNA structure for helicase loading and translocation along DNA in a 5' to 3' direction (PubMed:18499658, PubMed:22102414).

The helicase activity is capable of displacing duplex regions up to 100 bp, which can be extended up to 500 bp by the replication protein A (RPA) or the cohesion CTF18-replication factor C (Ctf18-RFC) complex activities (PubMed:18499658).

Shows also ATPase- and helicase activities on substrates that mimic key DNA intermediates of replication, repair and homologous recombination reactions, including forked duplex, anti-parallel G-quadruplex and three-stranded D-loop DNA molecules (PubMed:22102414, PubMed:26503245).

Plays a role in DNA double-strand break (DSB) repair at the DNA replication fork during DNA replication recovery from DNA damage (PubMed:23797032).

Recruited with TIMELESS factor upon DNA-replication stress response at DNA replication fork to preserve replication fork progression, and hence ensure DNA replication fidelity (PubMed:26503245).

Cooperates also with TIMELESS factor during DNA replication to regulate proper sister chromatid cohesion and mitotic chromosome segregation (PubMed:17105772, PubMed:18499658, PubMed:20124417, PubMed:23116066, PubMed:23797032).

Stimulates 5'-single-stranded DNA flap endonuclease activity of FEN1 in an ATP- and helicase-independent manner; and hence it may contribute in Okazaki fragment processing at DNA replication fork during lagging strand DNA synthesis (PubMed:18499658).

Its ability to function at DNA replication fork is modulated by its binding to long non-coding RNA (lncRNA) cohesion regulator non-coding RNA DDX11-AS1/CONCR, which is able to increase both DDX11 ATPase activity and binding to DNA replicating regions (PubMed:27477908).

Plays also a role in heterochromatin organization (PubMed:21854770).

Involved in rRNA transcription activation through binding to active hypomethylated rDNA gene loci by recruiting UBTF and the RNA polymerase Pol I transcriptional machinery (PubMed:26089203).

Plays a role in embryonic development and prevention of aneuploidy (By similarity).

Involved in melanoma cell proliferation and survival (PubMed:23116066).

Associates with chromatin at DNA replication fork regions (PubMed:27477908).

Binds to single- and double-stranded DNAs (PubMed:9013641, PubMed:18499658, PubMed:22102414).

(Microbial infection) Required for bovine papillomavirus type 1 regulatory protein E2 loading onto mitotic chromosomes during DNA replication for the viral genome to be maintained and segregated.

Cellular response to bleomycin Source: UniProtKB
Cellular response to cisplatin Source: UniProtKB
Cellular response to DNA damage stimulus Source: UniProtKB
Cellular response to hydroxyurea Source: UniProtKB
DNA duplex unwinding Source: UniProtKB
DNA repair Source: UniProtKB-KW
Establishment of sister chromatid cohesion Source: GO_Central
G-quadruplex DNA unwinding Source: UniProtKB
IRE1-mediated unfolded protein response Source: Reactome
Multicellular organism development Source: UniProtKB-KW
Negative regulation of protein binding Source: UniProtKB
Nucleolar chromatin organization Source: UniProtKB
Positive regulation of chromatin binding Source: UniProtKB
Positive regulation of double-strand break repair Source: UniProtKB
Positive regulation of endodeoxyribonuclease activity Source: UniProtKB
Positive regulation of sister chromatid cohesion Source: UniProtKB
Positive regulation of transcription of nucleolar large rRNA by RNA polymerase I Source: UniProtKB
Replication fork processing Source: UniProtKB
Sister chromatid cohesion Source: UniProtKB
Viral process Source: UniProtKB-KW

Spindle pole; Centrosome; Nucleus; Nucleolus; Midbody. During the early stages of mitosis, localizes to condensed chromatin and is released from the chromatin with progression to metaphase. Also localizes to the spindle poles throughout mitosis and at the midbody at later stages of mitosis (metaphase to telophase) (PubMed:17105772). In interphase, colocalizes with nucleolin in the nucleolus (PubMed:26089203).
Chromosome. (Microbial infection) Colocalizes with bovine papillomavirus type 1 regulatory protein E2 on mitotic chromosomes at early stages of mitosis.

Warsaw breakage syndrome (WBRS):
A syndrome characterized by severe microcephaly, pre- and postnatal growth retardation, facial dysmorphism and abnormal skin pigmentation. Additional features include high arched palate, coloboma of the right optic disk, deafness, ventricular septal defect, toes and fingers abnormalities. At cellular level, drug-induced chromosomal breakage, a feature of Fanconi anemia, and sister chromatid cohesion defects, a feature of Roberts syndrome, coexist.